(Diethylamino)sulfur trifluoride → rac-(3S,5S)-5-(2,6-dimethoxyphenyl)-3-fluoro-1-(4-(trifluoromethoxy)benzyl)pyrrolidin-2-one

HRID 594405Notes

Reaction equation

CCN(S(F)(F)[F:7])CC.[CH3:10][O:11][C:12]1[CH:17]=[CH:16][CH:15]=[C:14]([O:18][CH3:19])[C:13]=1[CH:20]1[N:24]([CH2:25][C:26]2[CH:31]=[CH:30][C:29]([O:32][C:33]([F:36])([F:35])[F:34])=[CH:28][CH:27]=2)[C:23](=[O:37])[CH:22](O)[CH2:21]1.C([O-])(O)=O.[Na+]>C(Cl)Cl>[CH3:19][O:18][C:14]1[CH:15]=[CH:16][CH:17]=[C:12]([O:11][CH3:10])[C:13]=1[CH:20]1[N:24]([CH2:25][C:26]2[CH:27]=[CH:28][C:29]([O:32][C:33]([F:35])([F:36])[F:34])=[CH:30][CH:31]=2)[C:23](=[O:37])[CH:22]([F:7])[CH2:21]1

Participants

Conditions

Temperature: 0 °C

Procedure

A cooled (−78° C.) mixture of DAST (117 mg; 0.72 mmol) in anh. DCM (0.5 ml) was treated dropwise with a solution of rac-(3R*,5S*)-5-(2,6-dimethoxyphenyl)-3-hydroxy-1-(4-(trifluoromethoxy)benzyl)-pyrrolidin-2-one (100 mg; 0.24 mmol) in anh. DCM (0.5 ml). The resulting mixture was further stirred at −78° C., under nitrogen, for 1 h, at 0° C. for 30 min., and finally at rt for 1 h. Aq. sat. NaHCO3 was added, and the resulting mixture was extracted with DCM. The mixed organic layers were dried over anh. MgSO4, filtered, and concentrated to dryness under reduced pressure. Purification by preparative HPLC afforded rac-(3S*,5S*)-5-(2,6-dimethoxyphenyl)-3-fluoro-1-(4-(trifluoromethoxy)benzyl)pyrrolidin-2-one as a colorless solid. LC-MS (conditions A): tR=0.90 min.; [M+H]+: 414.12 g/mol.

Workup

temperatureA cooled
waitfinally at rt for 1 h
extractionthe resulting mixture was extracted with DCM
dry with materialThe mixed organic layers were dried over anh. MgSO4
filtrationfiltered
concentrationconcentrated to dryness under reduced pressure
customPurification by preparative HPLC

Sources & evidence

ORD record: ord-c0b9d84504a04bdc85d64d379bc519cb
Source dataset: uspto-grants-2016_01
DOI: 10.6084/m9.figshare.5104873.v1
Patent number: US09242970B2

Reaction notes

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