Subscribe to RSS
DOI: 10.1055/s-0030-1260584
Highly Efficient Carbamate Formation from Alcohols and Hindered Amino Acids or Esters Using N,N′-Disuccinimidyl Carbonate (DSC)
Publication History
Publication Date:
26 May 2011 (online)
Abstract
A highly efficient and straightforward protocol to prepare carbamates from alcohols and hindered amino acids/esters mediated by N,N′-disuccinimidyl carbonate (DSC) in the presence of catalytic amount of pyridine is described. This method could be carried out under mild conditions in one pot, and a wide variety of carbamates were obtained in high yield with excellent purity.
Key words
carbamate - N,N′-disuccinimidyl carbonate - DSC - hindered amino acids/esters - pyridine
-
1a
Adams P.Baron FA. Chem. Rev. 1965, 65: 567 -
1b
Ray S.Chaturvedi D. Drugs Future 2004, 29: 343 -
1c
Ray S.Pathak SR.Chaturvedi D. Drugs Future 2005, 30: 161 -
1d
Mateen A.Chapalamadugu S.Kashar B.Bathi AR.Chaudhary GR. Biol. Degrad. Biorem. Toxic. Chem. 1994, 198 -
1e
Wigfield YY. Food Sci. Technol. (NY) 1996, 77: 1501 -
2a
McCauley JA.McIntyre CJ.Rudd MT.Nguyen KT.Romano JJ.Butcher JW.Gilbert KF.Bush KJ.Holloway K.Swestock J.Wan B.Carroll SS.DiMuzio JM.Graham DJ.Ludmerer SW.Mao S.Stahlhut MW.Fandozzi CM.Trainor N.Olsen DB.Vacca JP.Liverton NJ. J. Med. Chem. 2010, 53: 2443 -
2b
Liverton NJ.Carroll SS.DiMuzio J.Fandozzi C.Graham DJ.Hazuda D.Holloway K.Ludmerer SW.McCauley JA.McIntyre CJ.Olsen DB.Rudd MT.Stahlhut M.Vacca JP. Antimicrob. Agents Chemother. 2010, 54: 305 -
2c
Holloway MK,Liverton NJ,Ludmerer SW,McCauley JA,Olsen DB,Rudd MT,Vacca JP, andMcIntyre CJ. inventors; US 7,470,664. -
2d
Belyk KM.Xiang B.Bulger PG.Leonard WR.Balsells J.Yin J.Chen C. Org. Process Res. Dev. 2010, 14: 692 -
3a
Montalbetti CAGN.Falque V. Tetrahedron 2005, 61: 10827 -
3b
D’Addona D.Bochet CG. Tetrahedron Lett. 2001, 42: 5227 -
3c
Grzyb JA.Shen M.Yoshina-Ishii C.Chi W.Brown RS.Batey RA. Tetrahedron 2005, 61: 7153 -
3d
Batey RA.Yoshina-Ishii C.Taylor SD.Santhakumar V. Tetrahedron Lett. 1999, 40: 2669 -
3e
Grzyb JA.Batey RA. Tetrahedron Lett. 2008, 49: 5279 -
3f
Davulcu AH.McLeod DD.Li J.Katipally K.Littke A.Doubleday W.Xu Z.McConlogue CW.Lai CJ.Gleeson M.Schwinden M.Parsons RL.
J. Org. Chem. 2009, 74: 4068 - 4
Ghosh AK.Duong TT.McKee SP.Thompson WJ. Tetrahedron Lett. 1992, 33: 2781 -
5a
Diamanti S.Arifuzzaman S.Elsen A.Genzer J.Vaia RA. Polymer 2008, 49: 3770 -
5b
Hamilton GA.Backes BJ. Tetrahedron Lett. 2006, 47: 967 -
5c
Alsina J.Rabanal F.Chiva C.Giralt E.Albericio F. Tetrahedron 1998, 54: 10125 - 7
Ototake N.Nakamura M.Dobashi Y.Fukaya H.Kitagawa O. Chem. Eur. J. 2009, 15: 5090
References and Notes
General Procedure
for Preparation of Carbamate 4
To a solution of alcohol 5 (0.5 g, 3.9 mmol) in anhyd DMF (3 mL)
was added DSC (1.2 g, 1.2 equiv) and pyridine (63 µL, 0.2
equiv). The mixture was heated and aged at 40 ˚C
for
15 h until complete activation of 5 was
observed as monitored by GC (>99% conversion).
The mixture was cooled to ambient temperature for addition of H2O
(3 mL), keeping temperature below 30 ˚C. l-tert-Leucine (0.53 g, 1.0 equiv) and
K3PO4 (1.66 g, 2 equiv), keeping the reaction temperature
below 30 ˚C. The reaction mixture was then stirred at ambient
temperature for 3-6 h until complete carbamate formation
was observed as monitored by HPLC or TLC. To the reaction mixture
was charged H2O (10 mL) and EtOAc (10 mL). The organic
layer was separated, and the aqueous layer was extracted with EtOAc
(5 mL). Both organic layers were combined, washed sequentially with
1 N HCl, H2O and brine, and dried (MgSO4).
Concentration of the organic solution afforded the carbamate 4 as an oil, amide rotamers exists by NMR
spectrum. ¹H NMR (500 MHz, CDCl3): δ = 0.93
(s, 6 H), 1.05 (s, 9 H), 1.35-1.38 (m, 2 H), 2.01-2.06
(m, 2 H), 3.80-3.82 (d, J = 10.0
Hz, 1 H), 3.87-3.89 (d, J = 10.0
Hz, 1 H), 3.98 (br, 0.3 H, minor rotamer), 4.21-4.23 (d, J = 10.0 Hz,
0.7 H, major rotamer), 4.93-4.95 (d, J = 10.0
Hz, 1 H), 5.01-5.04 (d, J = 15.0
Hz, 1 H), 5.27-5.29 (d, J = 10.0
Hz, 0.7 H, major rotamer), 5.78-5.86 (m, 1 H), 6.21-6.22
(br, 0.3 H, minor rotamer). ¹³C NMR
(125 MHz, CDCl3): δ = 24.1, 24.3 (minor
rotamer), 26.5, 26.9 (minor rotamer), 28.30, 34.0, 34.6, 38.2, 62.0, 63.3
(minor rotamer), 73.2, 73.9 (minor rotamer), 114.1, 139.2, 139.9
(minor rotamer), 156.7, 176.4, 177.2 (minor rotamer).