Water → (S)-3-(4-bromo-2-hydroxy-phenyl)-pyrrolidine-1-carboxylic acid tert-butyl ester

HRID 503924Notes

Reaction equation

C([S-])C.[Na+].[C:5]([O:9][C:10]([N:12]1[CH2:16][CH2:15][C@@H:14]([C:17]2[CH:22]=[CH:21][C:20]([Br:23])=[CH:19][C:18]=2[O:24]C)[CH2:13]1)=[O:11])([CH3:8])([CH3:7])[CH3:6].OS([O-])(=O)=O.[K+].[O-]S([O-])(=O)=O.[Na+].[Na+].O>CN(C=O)C>[C:5]([O:9][C:10]([N:12]1[CH2:16][CH2:15][C@@H:14]([C:17]2[CH:22]=[CH:21][C:20]([Br:23])=[CH:19][C:18]=2[OH:24])[CH2:13]1)=[O:11])([CH3:8])([CH3:6])[CH3:7]

Participants

Conditions

Temperature: 105 °C

Procedure

Sodium ethanethiolate (80%, 218.7 mg, 1.704 mmol) was added to a solution of (S)-3-(4-bromo-2-methoxy-phenyl)-pyrrolidine-1-carboxylic acid tert-butyl ester (303 mg, 0.8505 mmol) in DMF (3.1 mL) under argon atmosphere. The reaction mixture was heated at 105° C. for 3.5 hours, then cooled to 5° C. A solution of 10% KHSO4/Na2SO4 was added until pH reached 2-3. Water was added, and the resulting mixture was extracted with EtOAc. The combined organic extracts were washed with water and brine, dried over Na2SO4, filtered, and evaporated under reduced pressure. The residue was purified via flash chromatography (hexane/EtOAc, with a gradient from 90/10 to 85/15) to give 236 mg (81% yield) of (S)-3-(4-bromo-2-hydroxy-phenyl)-pyrrolidine-1-carboxylic acid tert-butyl ester as a foam.

Workup

temperaturecooled to 5° C
extractionthe resulting mixture was extracted with EtOAc
washThe combined organic extracts were washed with water and brine
dry with materialdried over Na2SO4
filtrationfiltered
customevaporated under reduced pressure
customThe residue was purified via flash chromatography (hexane/EtOAc

Sources & evidence

ORD record: ord-f026644fd6714ffe8ed5dce0271dbc28
Source dataset: uspto-grants-2010_08
DOI: 10.6084/m9.figshare.5104873.v1
Patent number: US07776910B2

Reaction notes

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