Download PDF
Synlett 2006(13): 2039-2042  
DOI: 10.1055/s-2006-948186
LETTER
© Georg Thieme Verlag Stuttgart · New York

Synthesis of 3,3-Difluoroazetidines

Willem Van Brabandt, Norbert De Kimpe*
Department of Organic Chemistry, Faculty of Bioscience Engineering, Ghent University, Coupure links 653, 9000 Ghent, Belgium
Fax: +32(9)2646243; e-Mail: norbert.dekimpe@UGent.be;
Further Information

Publication History

Received 19 April 2006
Publication Date:
09 August 2006 (online)

    Permissions and Reprints All articles of this category

Abstract

A high-yield synthesis of 3,3-difluoroazetidines was developed by a monochlorohydroalane reduction of 3,3-difluoroazetidin-2-ones. The latter compounds were conveniently synthesized by a Reformatsky-type reaction of aldimines with ethyl bromo­difluoroacetate.

Key words

3,3-difluoroazetidines - 3,3-difluoroazetidin-2-ones - aldimines - Reformatsky - monochlorohydroalane

    References and Notes

  • 1 Smart B. J. Fluorine Chem.  2001,  109:  3 
    CrossrefSearch in Google Scholar
  • 2 Welch JT. Tetrahedron  1987,  43:  3123 
    CrossrefSearch in Google Scholar
  • 3 Parker JC, and Hulin B. inventors; US  2005043292 A1.  ; Chem. Abstr. 2005, 142, 261783
  • 4 Li W, Oliver E, Rojas C, Kalish V, and Belyakov S. inventors; WO 2004071454  A2.  ; Chem. Abstr. 2004, 141, 225299
  • 5 Duffy JL, Mathvink RJ, Weber AE, and Xu J. inventors; WO  2004050022 A2.  ; Chem. Abstr. 2004, 141, 54612
  • 6 Colandrea VJ, Edmondson SD, Mathvink RJ, Mastracchio A, Weber AE, and Xu J. inventors; WO  2004043940 A1.  ; Chem. Abstr. 2004, 141, 7438
  • 7 Hulin B, and Parker JC. inventors; WO  2003101958 A2.  ; Chem. Abstr. 2003, 140, 16965
  • 8 Weber A. J. Med. Chem.  2004,  47:  4135 
    CrossrefSearch in Google Scholar
  • 9 Ge P, Horvath RF, Zhang LY, Yamaguchi Y, Kaiser B, Zhang X, Zhang S, Zhao H, John S, Moorcroft N, and Shutske G. inventors; WO  2005023806 A2.  ; Chem. Abstr. 2005, 142, 261783
  • 10 Brooks DP. inventors; WO  2005000311 A1.  ; Chem. Abstr. 2005, 142, 114098
  • 11 Flohr A, and Norcross RD. inventors; US  2004204584 A1.  ; Chem. Abstr. 2004, 141, 350158
  • 12 Churcher I, Harrison T, Kerrad S, Oakley PJ, Shaw DE, Teall MR, and Williams S. inventors; WO  2004031137 A1.  ; Chem. Abstr. 2004, 140, 321108
  • 13 Collins IJ, Cooper LC, Harrison T, Keown LE, Madin AR, and Mark P. inventors; WO  2003093252 A1.  ; Chem. Abstr. 2003, 139, 16965
  • 14 Provins L, Van Keulen BJ, Surtees J, Talaga P, and Christophe B. inventors; WO  2003087064 A1.  ; Chem. Abstr. 2003, 139, 337980
  • 15 Borthwick AD, Hatley RJ, Hickey DMB, Liddle J, Livermore DGH, Mason AM, Miller ND, Nerozzi F, Sollis SL, Szardenings AK, and Wyatt PG. inventors; WO  2003053433A1.  ; Chem. Abstr. 2003, 139, 85377
  • 16 Selnick HG, Barrow JC, Nantermet PG, Williams PD, Stauffer KJ, Sanderson PE, Rittle KE, Morissette MM, Wiscount CM, Tran LO, Lyle TA, and Staas DD. inventors; WO  2002050056 A1.  ; Chem. Abstr. 2002, 137, 63475
  • 17 Carling WR, Mitchinson AR, Michail GN, and Street LJ. inventors; WO  2000047582 A1.  ; Chem. Abstr. 2000, 133, 177176
  • 18 Banks RE. Barlow MG. Haszeldine RN. J. Chem. Soc.  1965,  6149 
  • 19 Banks RE. Haszeldine RN. Matthews V. J. Chem. Soc.  1967,  2263 
  • 20 Yamamoto T. Yasuhara A. Shiraishi F. Kaya K. Abe T. Chemosphere  1997,  35:  643 
    CrossrefSearch in Google Scholar
  • 21 Chambers RD. Shepherd T. Tamura M. J. Chem. Soc., Perkin Trans. 1  1990,  975 
    Crossref
  • 22 Lacroix S. Chequillaume A. Gérard S. Marchand-Brynaert J. Synthesis  2003,  2483 ; and references cited therein
    Thieme Connect
  • 23 Marcotte S. Pannecoucke X. Feasson C. Quirion J.-C. J. Org. Chem.  1999,  64:  8461 
    CrossrefSearch in Google Scholar
  • 24 Duboc R. Hénaut C. Savignac M. Genet J.-P. Bhatnagar N. Tetrahedron Lett.  2001,  42:  2461 
    CrossrefSearch in Google Scholar
  • 25 Ojima I. Zhao M. Yamato T. Nakahashi K. J. Org. Chem.  1991,  56:  5263 
    CrossrefSearch in Google Scholar
26

Synthesis of 3,3-Difluoroazetidines 4-6 and 9 via the Reformatsky-Type Reaction. As an example, the synthesis of 1-benzyl-3,3-difluoro-4-phenylazetidin-2-one(5) is described. To a refluxing suspension of freshly activated Zn dust (1.63 g, 25 mmol) in dry THF (10 mL) was added a solution of 2 (0.98 g, 5 mmol) and ethyl bromodifluoroacetate (1.52, 7.5 mmol) in THF at such a rate so as to maintain vigorous reflux. After 1 h of reflux, the reaction mixture was cooled and extracted with CH2Cl2 (2 × 20 mL). The combined organic extracts were dried (MgSO4) and concentrated under vacuum. The residue was then purified by flash column chromatography over silica gel.
Preparation of Activated Zn Dust.
Nitrogen gas was bubbled through a mixture of 100 g (1.53 mol) of zinc and 250 mL of distilled H2O. After 15 min of stirring, 7.5 g (46 mmol) of CuSO4 was added, and the resulting mixture was stirred for 45 min under nitrogen atmosphere. At the same time, 500 mL of distilled H2O and 500 mL of acetone were degassed by stirring under a nitrogen atmosphere during 45 min. In order to remove the formed ZnSO4, the Zn-Cu couple was filtered off and washed with 500 mL of degassed H2O and 500 mL of degassed acetone (to remove the water). After evaporation of the solvent in vacuo, the activated Zn thus obtained was used immediately in the cyclocondensation reaction above.
1-Benzyl-3,3-difluoro-4-phenylazetidin-2-one ( 5): 82% yield; TLC: R f = 0.15 (PE-EtOAc, 10:1). 1H NMR (300 MHz, CDCl3): δ = 3.93 (1 H, dd, J = 14.6, 2.2 Hz, NCH), 4.72 [1 H, dd, J = 7.4, 2.2 Hz, NC(H)H], 4.95 [1 H, d, J = 14.6 Hz, NC(H)H], 7.09-7.45 (10 H, m, 2 × C6H5). 13C NMR (75 MHz, CDCl3): δ = 44.22 (NCH2), 68.00 (dd, J = 26.5, 24.2 Hz, NCH), 120.59 (dd, J = 292.6, 290.2 Hz, CF2), 128.08, 128.44, 128.60, 129.06, 129.09 and 129.84 (2 × CC 5H5), 129.99 and 133.38 (2 × CC5H5), 160.94 (t, J = 30.6 Hz, C=O). 19F NMR (282 Hz, CDCl3): δ = -114.18 (dd, J = 223.7, J = 7.0 Hz), -120.78 (d, J = 223.7 Hz). IR (NaCl): νmax = 3034, 2926, 1789, 1496, 1457 cm-1. MS (70 eV): m/z (%) = 274 (10) [M+ + 1]. Anal. Calcd for C16H13F2NO: C, 70.32; H, 4.79; N, 5.13. Found: C, 70.51; H, 4.91; N, 4.89.
1-Allyl-3,3-difluoro-4-phenylazetidin-2-one ( 6): 87% yield; TLC: R f = 0.25 (PE-EtOAc, 10:1). 1H NMR (300 MHz, CDCl3): δ = 3.47-3.55 [1 H, m, NC(H)H], 4.29 [1 H, dd, J = 15.4, 5.2 Hz, NC(H)H], 4.94 (1 H, dd, J = 7.4, 2.2 Hz, NCH), 5.11-5.26 (2 H, m, CH=CH 2), 5.67-5.80 (1 H, m, CH=CH2), 7.27-7.32 and 7.42-7.46 (5 H, 2 m, C6H5). 13C NMR (75 MHz, CDCl3): δ = 42.78 (NCH2), 68.37 (t, J = 24.8 Hz, NCH), 120.31 (CH2=CH), 120.62 (dd, J = 293.1, 289.6 Hz, CF2), 128.02, 129.05 and 129.86 (CC 5H5), 129.49 (CH=CH2), 130.21 (CC5H5), 160.93 (t, J = 30.6 Hz, C=O). 19F NMR (282 Hz, CDCl3): δ = -114.13 (dd, J = 223.7, 7.4 Hz), -121,43 (d, J = 223.7 Hz). IR (NaCl): νC=O = 1688, 1684 cm-1. MS (70 eV): m/z (%) = 224 (100) [M+ + 1]. Anal. Calcd for C12H11F2NO: C, 64.57; H, 4.97; N, 6.27. Found: C, 64.40; H, 5.15; N, 6.41.
1-Allyl-3,3-difluoro-4-isopropylazetidin-2-one ( 9): 53% yield; TLC: R f = 0.1 (PE-EtOAc, 10:1). 1H NMR (300 MHz, CDCl3): δ = 1.02 [3 H, dd, J = 6.9, 0.8 Hz, CH(CH 3)CH3], 1.07 [3 H, d, J = 6.9 Hz, CH(CH3)CH 3], 2.03 [1 H, octet, J = 6.9 Hz, CH(CH3)2], 3.66-3.77 [2 H, m, NC(H)H and NCH], 4.27 [1 H, ddt, J = 15.7, 5.0, 1.7 Hz, NC(H)H], 5.24-5.34 (2 H, m, CH=CH 2), 5.70-5.83 (1 H, m, CH=CH2). 13C NMR (75 MHz, CDCl3): δ = 18.21 and 18.25 (2 × CH3), 18.84 [CH(CH3)2], 44,34 (NCH2), 70.87 (t, J = 22.5 Hz, NCH), 119.73 (CH2=CH), 120.62 (dd, J = 290.8, 283.8 Hz, CF2), 130.39 (CH=CH2), 161.28 (t, J = 30.6 Hz, C=O). 19F NMR (282 Hz, CDCl3): δ = -113.96 (dd, J = 223.4, 9.5 Hz), -124.56 (d, J = 223.4 Hz). IR (NaCl): νC=O = 1794, νmax = 2971, 2938, 1645, 1473 cm-1. MS (70 eV): m/z (%) = 190 (100) [M+ + 1]. Anal. Calcd for C9H13F2NO: C, 57.13; H, 6.93; N, 7.40. Found: C, 57.29; H, 7.14; N, 7.68.
Ethyl 3-(Allylamino)-2,2-difluoro-4-methylpentanoate ( 10): 5% yield; TLC: R f = 0.25 (PE-EtOAc, 10:1). 1H NMR (300 MHz, CDCl3): δ = 0.98 and 1.06 [6 H, 2 d, J = 6.88 Hz, CH(CH 3)2], 1.35 (3 H, t, J = 7.15 Hz, CH2CH 3), 2.03 [1 H, septd, J = 6.9, 4.4 Hz, CH(CH3)2], 3.01 (1 H, ddd, J = 20.6, 9.4, 4.4 Hz, NHCH), 3.32 [1 H, dd, J = 14.0, 5.8 Hz, NHC(H)H], 3.39 [1 H, dd, J = 14.0, 6.3 Hz, NHC(H)H], 4.31 (2 H, q, J = 7.2 Hz, OCH 2), 5.03-5.20 (2 H, m, CH 2=CH), 5.73 (1 H, m, CH2=CH). 13C NMR (75 MHz, CDCl3): δ = 13.99 (CH3CH2O), 17.62 and 21.10 [CH(CH3)2], 28.00 [CH(CH3)2], 52.14 (NHCH2), 62.51 (OCH2), 63.32 (dd, J = 24.2, 20.8 Hz, NHCH), 115.88 (CH2=CH), 117.66 (t, J = 257.29 Hz),136.82 (CH2=CH), 164.77 (t, J = 32.31 Hz, C=O). 19F NMR (282 Hz, CDCl3): δ = -107.19 (dd, J = 254.9, 9.5 Hz), -117.44 (dd, J = 254.9, 20.8 Hz). IR (NaCl): νC=O = 1773, 1758, νmax = 2966, 1468 cm-1. MS (70 eV): m/z (%) = 236 (100) [M+ + 1]. Anal. Calcd for C11H19F2NO2: C, 56.16; H, 8.14; N, 5.95. Found: C, 55.82; H, 8.31; N, 5.75.

27

Synthesis of 3,3-Difluoroazetidines 6 and 11 via N-Alkylation of Difluoro-β-lactam ( 7).
As an example, the synthesis of 1-allyl-3,3-difluoro-4-phenylazetidin-2-one(6) is described. 3,3-Difluoroazetidin-2-one 7 (0.18 g, 1 mmol) was added to a solution of allyl bromide (0.15 g, 1.1 mmol), NaI (0.013 g, 0.1 mmol), n-Bu4NHSO4 (0.14 g, 0.4 mmol) and KOH (0.11 g, 2 mmol) in THF (10 mL). In the case of 3,3-difluoroazetidine 6, 1 h stirring at r.t. proved to be sufficient to complete the reaction. Then, 1.5 h of reflux was needed to complete the reaction in the case of azetidin-2-one 11. Subsequently, the mixture was poured in H2O (20 mL), and the reaction mixture was extracted three times with Et2O (20 mL). The organic extracts were combined, dried over MgSO4 and concentrated under vacuum. The residue was then purified by flash column chromatography.
1-Butyl-3,3-difluoro-4-phenylazetidin-2-one ( 11): 45% yield; TLC: R f = 0.15 (PE-EtOAc, 20:1). 1H NMR (300 MHz, CDCl3): δ = 0.90 (3 H, t, J = 7.3 Hz, CH3), 1.26-1.39 (2 H, m, CH3CH 2), 1.52 (2 H, quint, J = 7.4 Hz, NCH2CH 2), 2.94-3.03 [1 H, m, NC(H)H], 3.56-3.80 [1 H, m, NC(H)H], 4.91 (1 H, dd, J = 7.2, 2.2 Hz, NCH), 7.26-7.33 and 7.44-7.47 (5 H, 2 m, C6H5). 13C NMR (75 MHz, CDCl3): δ = 13.48 (CH3), 20.08 (CH3 CH2), 29.06 (NCH2 CH2), 40.16 (NCH2), 68.74 (t, J = 24.8 Hz, NCH), 120.50 (dd, J = 293.1, 289.6 Hz, CF2), 128.01, 129.05 and 129.86 (CC 5H5), 130.45 (CC5H5), 161.22 (t, J = 30.0 Hz, C=O). 19F NMR (282 Hz, CDCl3): δ = -114.38 (dd, J = 223.7, 7.8 Hz), -121.77 (d, J = 223.7 Hz). IR (NaCl): νC=O = 1788 cm-1. MS (70 eV): m/z (%) = 240 (100) [M+ + 1]. Anal. Calcd for C13H15F2NO: C, 65.26; H, 6.32; N, 5.85. Found: C, 65.04; H, 6.39; N, 5.68.

28

Synthesis of 3,3-Difluoroazetidines 12-16.
As an example, the synthesis of 1-allyl-3,3-difluoro-4-phenylazetidine (14) is described. LiAlH4 (0.57 g, 0.015 mmol) was added to AlCl3 (2.01 g, 0.015 mmol) in Et2O (30 mL) at 0 °C. After 30 min stirring at r.t., 3,3-difluoro-azetidin-2-one 6 (1.12 g, 0.005 mmol) was added to the reaction mixture. After 4 h of stirring at r.t., H2O was added until all LiAlH4 was neutralized. The solvent was decanted and the resulting suspension was extracted three times with Et2O (20 mL). The organic layers were combined, dried over MgSO4 and concentrated under vacuum, yielding pure
1-allyl-3,3-difluoro-4-phenylazetidine (14).
3,3-Difluoro-1-(4-methoxybenzyl)-4-phenylazetidine ( 12): 87% yield. 1H NMR (300 MHz, CDCl3): δ = 3.21 [1 H, ddd, J = 15.7, 13.5, 9.5 Hz, NC(H)HCF2], 3.48 [1 H, dd, J = 12.8, 2.2 Hz, NC(H)HC6H4], 3.65-3.74 [1 H, m, NC(H)HCF2], 3.78 (3 H, s, CH3O), 3.95 [1 H, d, J = 12.9 Hz, NC(H)HC6H4], 4.44 (1 H, dd, J = 14.9, 10.5 Hz, NCH), 6.82-6.87 (2 H, m, 2 × MeOCCH), 7.21-7.49 (7 H, m, C6H5 and 2 × NCH2CCH). 13C NMR (75 MHz, CDCl3): δ = 55.26 (CH3O), 60.32 (NCH2C6H4), 61.42 (t, J = 22.6 Hz, CH2CF2), 76.68 (t, J = 32.3 Hz, NCH), 113.81 (2 × CH3OCCH), 117.03 (t, J = 279.8 Hz, CF2), 127.87, 128.33, 128.44 and 129.90 (CC 5H5 and 2 × MeOCCHCH), 129.09 and 134.07 (NCHC and NCH2 C), 159.02 (MeOC). 19F NMR (282 Hz, CDCl3): δ = -116.65 (ddt, J = 190.7, 15.6, 10.4 Hz), -91.78 (dtd, J = 190.7, 14.3, 6.5 Hz). IR (NaCl): νmax = 2959, 2935, 2838, 1613, 1513, 1454, 1331 cm-1. MS (70 eV): m/z (%) = 290 (10) [M+ + 1], 121 (100). Anal. Calcd for C17H17F2NO: C, 70.57; H, 5.92; N, 4.84. Found: C, 70.71; H, 5.78; N, 4.60.
1-Benzyl-3,3-difluoro-4-phenylazetidine ( 13): 84% yield. 1H NMR (300 MHz, CDCl3): δ = 3.24 [1 H, ddd, J = 15.7, 13.5, 9.5 Hz, NC(H)HCF2], 3.47 [1 H, dd, J = 13.1, 1.9 Hz, NC(H)HC6H5], 3.68 [1 H, tdd, J = 9.6, 6.6, 1.5 Hz, NC(H)HCF2], 3.96 [1 H, d, J = 13.1 Hz, NCH(H)C6H5], 4.44 (1 H, dd, J = 14.9, 10.5 Hz NCH), 7.18-7.49 (10 H, m, 2 × C6H5). 13C NMR (75 MHz, CDCl3): δ = 60.94 (NCH2C6H5), 61.65 (dd, J = 24.2, 20.8 Hz, CH2CF2), 76.87 (t, J = 22.5 Hz, NCH), 117.01 (t, J = 279.2 Hz, CF2), 127.43, 127.87, 128.31, 128.39, 128.45 and 128.62 (2 × CC 5H5), 133.96 (NCHC), 137.08 (NCH2 C). 19F NMR (282 Hz, CDCl3): δ = -117.00 (ddt, J = 190.7, 15.6, 10.4 Hz), -91.82 (dtd, J = 190.7, 13.9, 6.9 Hz). IR (NaCl): νmax = 3064, 3031, 2970, 2925, 2855, 2802, 1604, 1496, 1453 cm-1. MS (70 eV): m/z (%) = 260 (20) [M+ + 1], 120 (100), 91 (20). Anal. Calcd for C16H15F2N: C, 74.11; H, 5.83; N, 5.40. Found: C, 74.01; H, 6.11; N, 5.27.
1-Allyl-3,3-difluoro-4-phenylazetidine ( 14): 87% yield. 1H NMR (300 MHz, CDCl3): δ = 3.13 [1 H, ddd, J = 13.4, 9.5, 1.0 Hz, NC(H)HCH=CH2], 3.31 [1 H, ddd, J = 15.6, 13.5, 9.5 Hz, NC(H)HCF2], 3.42 [1 H, ddt, J = 13.4, 5.5, 1.4 Hz, NC(H)HCH=CH2], 3.84 [1 H, tdd, J = 9.5, 6.9, 1.5 Hz, NC(H)HCF2], 4.44 (1 H, ddd, J = 15.1, 10.2, 0.8 Hz, NCH), 5.08-5.26 (2 H, m, CH=CH 2), 5.72-5.85 (1 H, m, CH=CH2), 7.25-7.46 (5 H, m, C6H5). 13C NMR (75 MHz, CDCl3): δ = 60.26 (NCH2CH=CH2), 61.80 (dd, J = 24.2, 20.8 Hz, CH2CF2), 77.03 (t, J = 22.5 Hz, NCH), 116.95 (t, J = 279.8 Hz, CF2), 118.04 (CH=CH2), 127.90, 128.31 and 128.44 (CC 5H5), 133.79 (CH=CH2), 134.21 (NCHC). 19F NMR (282 Hz, CDCl3): δ = -116.33 (ddt, J = 190.7, 15.6, 10.4 Hz), -91.63 (dtd, J = 190.7, 14.7, 6.9 Hz). IR (NaCl): νmax = 3067, 3031, 2977, 2925, 2857, 2807, 1644, 1497, 1459, 1452 cm-1. MS (70 eV): m/z (%) = 210 (20) [M+ + 1], 190 (80), 88 (100). Anal. Calcd for C12H13F2N: C, 68.88; H, 6.26; N, 6.69. Found: C, 69.09; H, 6.10; N, 6.53.
3,3-Difluoro-4-phenylazetidine ( 15): 82% yield. 1H NMR (300 MHz, CDCl3): δ = 3.79 [1 H, ddd, J = 22.0, 10.5, 1.7 Hz, NC(H)HCF2], 4.04 [1 H, ddd, J = 14.9, 13.5, 10.5 Hz, NC(H)HCF2], 5.14 (1 H, dd, J = 14.9, 10.5 Hz, NCH), 7.22-7.44 (5 H, m, C6H5). 13C NMR (75 MHz, CDCl3): δ = 56.08 (t, J = 24.2 Hz, NHCH2), 71.04 (t, J = 23.7 Hz, NHCH), 119.21 (t, J = 282.1 Hz, CF2), 127.29, 128.34 and 128.40 (CC 5H5), 135.46 (NHCHC). 19F NMR (282 Hz, CDCl3): δ = -91.22 (dq, J = 189.9, 12.9 Hz), -110.18 (ddt, J = 189.9, 14.7, 11.3 Hz). IR (NaCl): νmax = 3347, 2948, 2879, 1514, 1497, 1459 cm-1. MS (70 eV): m/z (%) = 170 (100) [M+ + 1]. Anal. Calcd for C9H9F2N: C, 63.90; H, 5.36; N, 8.28. Found: C, 64.14; H, 5.25; N, 8.43.
1-Allyl-3,3-difluoro-4-isopropylazetidine ( 16): 53% yield. 1H NMR (300 MHz, CDCl3): δ = 0.92 and 0.95 (6 H, 2 d, J = 6.7 Hz, 2 × CH3), 1.96-2.08 [1 H, m, CH(CH3)2], 2.89-3.01 [2 H, m, NCH and NC(H)HCH=CH2], 3.10 [1 H, td, J = 15.4, 10.2 Hz, NC(H)HCF2], 3.51 [1 H, ddt, J = 13.4, 5.1, 1.5 Hz, NC(H)HCH=CH2], 3.70 [1 H, tdd, J = 10.5, 10.2, 1.5 Hz, NC(H)HCF2], 5.12-5.24 (2 H, m, CH=CH 2), 5.74-5.87 (1 H, m, CH=CH2). 13C NMR (75 MHz, CDCl3): δ = 18.54 and 18.76 (2 × CH3), 28.83 [CH(CH3)2], 61.94 (dd, J = 25.4, 20.8 Hz, CH2CF2), 62.28 (NCH2CH=CH2), 80.37 (dd, J = 21.9, 19.6 Hz, NCH), 117.7 (t, J = 278.1 Hz, CF2), 118.21 (CH=CH2), 133.81 (CH=CH2). 19F NMR (282 Hz, CDCl3): δ = -117.80 (dtd, J = 197.7, 16.5, 8.7 Hz), -88.64 (ddt, J = 197.7, 14.7, 10.0 Hz). IR (NaCl): νmax = 2964, 2931, 2875, 2803, 1645, 1472, 1458 cm-1. MS (70 eV):
m/z (%) = 176 (100) [M+ + 1]. Anal. Calcd for C9H15F2N: C, 61.69; H, 8.63; N, 7.99. Found: C, 61.53; H, 8.69; N, 7.89.