tert-Butyl methyl ether → HCID 68647086, compound

HRID 1162696Notes

Reaction equation

HRID 1162696 reaction equation
[C:1]([O:5][C:6]([N:8]1[CH2:12][CH:11]([OH:13])[CH:10]([C:14]#[N:15])[CH2:9]1)=[O:7])([CH3:4])([CH3:3])[CH3:2].[C:16]([O:20]C)(C)(C)[CH3:17]>C(OC=C)(=O)C>[C:1]([O:5][C:6]([N:8]1[CH2:9][C@@H:10]([C:14]#[N:15])[C@H:11]([O:13][C:16](=[O:20])[CH3:17])[CH2:12]1)=[O:7])([CH3:4])([CH3:2])[CH3:3]

Participants

4

Reactant 2

HCID 15413tert-Butyl methyl etherHCID 107985871-Boc-3-Cyano-4-hydroxypyrrolidine

Product 1

HCID 68647086HCID 68647086, compound

Reagents, catalysts & solvents 1

HCID 7904Vinyl AcetateSolvent

Conditions

Temperature
22 °C

Procedure

79.1 To a solution of 17.1 g (98.2% GC purity) of trans, rac-3-cyano-4-hydroxy-pyrrolidine-1-carboxylic acid tert-butyl ester (prepared according to C. Y. Hong et al. (Bioorganic Medicinal Chemistry Letters, 2003, 13, 4399), by D. J. Kim et al. (Journal of Medicinal Chemistry, 1997, 40, 3584) or by S. U. Hansen & M. Bols (Acta Chemica Scandinavica, 1997, 52, 1214)) in 765 ml of t-butylmethyl ether and 85 ml of vinyl acetate was added 21.3 g of Lipase AK (Amano Enzyme Inc.) and the suspension was stirred at 22° C. until ca. 54% conversion (as calculated from the ee-values of substrate and product according to C. J. Sih et al. (J. Am. Chem. Soc., 1982, 104, 7294)) was reached. The enzyme was filtered off, the filtrate evaporated in vacuo and the residual oil chromatographed on 400 g silicagel (0.040-0.063 mm; dichloromethane/diethyl ether 9:1→3:1) to give the formed optically enriched (S,S)-3-acetoxy-4-cyano-pyrrolidine-1-carboxylic acid tert-butyl ester (10.7 g; 84% ee, optically further enriched in example 60.2) and the retained (R,R)-3-cyano-4-hydroxy-pyrrolidine-1-carboxylic acid tert-butyl ester (6.9 g). Analytics: +EI-MS: 213.3 (M+H+); [α]D=+1.20° (c=1.00, CHCl3); 97.8% ee (GC on BGB-176; 30 m×0.25 mm; H2; 90 kPa; 130° C. to 200° C. with 2° C./min; inj. 200° C.).

Workup

  1. filtrationThe enzyme was filtered off
  2. customthe filtrate evaporated in vacuo
  3. customthe residual oil chromatographed on 400 g silicagel (0.040-0.063 mm; dichloromethane/diethyl ether 9:1→3:1)
  4. customto give the

Sources & evidence

ORD record
ord-f127d07c47044cd9ac7c51bde5a0b2a0
Source dataset
uspto-grants-2010_10
Patent number
US07820699B2

Reaction notes

Loading…