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DOI: 10.1055/s-0031-1290092
A Mild Method for the Cleavage of the 4-Picolyloxy Group with Magnesium under Neutral Conditions
Publikationsverlauf
Publikationsdatum:
09. Dezember 2011 (online)
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Abstract
A mild and efficient method for the selective hydrolysis of 4-picolyl esters with magnesium in methanol or water in the presence of other esters and sensitive protecting groups is described. 4-Picolyl aryl ethers and thioethers are also smoothly deprotected to give the corresponding phenols and thiophenols.
Key words
hydrolysis - 4-picolyloxy group - magnesium - protecting groups - phenols
- Supporting Information for this article is available online:
- Supporting Information
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Protective
Groups in Organic Synthesis
3rd ed.:
Green TW.Wuts PGM. Wiley; New York: 1999. p.373-377
References and Notes
Typical Procedure
A: Protection
A solution of N-Boc-l-alanine-l-valine
(0.864 g, 3 mmol), 4-picolyl chloride hydrochloride (0.50 g, 3 mmol),
and Et3N (0.606 g, 6 mmol) in DMF (10 mL) was heated
at 90 ˚C for 3 h, till TLC showed the absence of 4-picolyl
chloride. The solvent was distilled off, and EtOAc (10 mL) was added
to the residue. The solution was washed with sat. NaHCO3 (3 × 10
mL), H2O (2 × 10 mL), and
brine (10 mL), and then dried over MgSO4. After evaporation
of the solvent, the dark brown solid was purified by column chromatography
using EtOAc-PE (1:1). The filtrate was evaporated in vacuo,
and the product was purified by column chromatography using EtOAc-PE
(1:1). Yield 0.852 g (75%); [α]D
²0 -24.6
(c 1, DMF). ESI-MS: m/z = 380.2 [M + H]+,
402.2 [M + Na]+. ESI-HRMS: m/z calcd for [C19H29N3O5 + H]+:
380.2185; found: 380.2181; m/z calcd
for [C19H29N3O5Na]+:
402.2005; found: 402.2002. ¹H NMR (400 MHz,
CDCl3): δ = 0.90 (d, J = 7.0
Hz, 3 H), 0.95 (d, J = 7.0
Hz, 3 H), 1.35 (d, J = 6.9 Hz,
3 H), 1.44 (s, 9 H), 2.20-2.24 (m, 1 H), 4.23 (s, 1 H), 4.61
(t, J = 5.0,
9.0 Hz, 1 H), 5.18 (s, 2 H), 5.28 (d, J = 7.9 Hz,
1 H), 7.26-7.30 (m, 2 H), 8.61 (m, 2 H). ¹³C
NMR (100 MHz, CDCl3): δ = 17.5, 18.9,
28.1, 30.9, 49.8, 57.0, 64.7, 80.0, 121.8, 140.2, 149.9, 155.6,
171.3, 172.7.
Typical Procedure B:
Deprotection
To a solution of picolyl N-Boc-l-alanine-l-valinate (0.76 g, 2 mmol) in MeOH (20
mL) magnesium turnings (288 mg, 12 mmol) were added. After stirring
for 4 h at r.t. the reaction mixture was filtered. The filtrate
was concentrated in vacuo, and the residue was diluted with 5% NaHCO3 (10
mL) and EtOAc (10 mL), and the organic layer was extracted with
5% NaHCO3 (2 × 10
mL). The aqueous extract was acidified to pH 2-3 with sat.
KHSO4 and extracted with EtOAc (2 × 10 mL).
The organic layer was washed with brine (2 × 10
mL), dried with Na2SO4, and filtered. The
residue was purified by silica gel column chromatography using EtOAc-PE.
Yield 0.518 g (90%); [α]D
²0 8.7
(c 1, CHCl3).