Pyridine → rac-(3R,5S)-3-chloro-5-(2,6-dimethoxyphenyl)-1-(4-(trifluoromethoxy)benzyl)pyrrolidin-2-one

HRID 594401Notes

Reaction equation

[CH3:1][O:2][C:3]1[CH:8]=[CH:7][CH:6]=[C:5]([O:9][CH3:10])[C:4]=1[CH:11]1[N:15]([CH2:16][C:17]2[CH:22]=[CH:21][C:20]([O:23][C:24]([F:27])([F:26])[F:25])=[CH:19][CH:18]=2)[C:14](=[O:28])[CH:13](O)[CH2:12]1.O=S(Cl)[Cl:32].N1C=CC=CC=1>O1CCOCC1>[Cl:32][CH:13]1[CH2:12][CH:11]([C:4]2[C:3]([O:2][CH3:1])=[CH:8][CH:7]=[CH:6][C:5]=2[O:9][CH3:10])[N:15]([CH2:16][C:17]2[CH:22]=[CH:21][C:20]([O:23][C:24]([F:27])([F:26])[F:25])=[CH:19][CH:18]=2)[C:14]1=[O:28]

Participants

Conditions

Temperature: 80 °C

Procedure

A solution of rac-(3S*,5S*)-5-(2,6-dimethoxyphenyl)-3-hydroxy-1-(4-(trifluoromethoxy)-benzyl)pyrrolidin-2-one (200 mg; 0.48 mmol) in dioxane (1 ml) was treated at rt successively with SOCl2 (69 mg; 0.58 mmol) and pyridine (46 mg; 0.58 mmol). The resulting mixture was then heated to 80° C. for 3 h. After cooling to rt, the mixture was concentrated under reduced pressure before water and AcOEt were added. The separated organic layer was washed with brine, dried over anh. MgSO4, filtered, and concentrated to dryness under reduced pressure. Purification by FC (DCM/MeOH=50/1) afforded rac-(3R*,5S*)-3-chloro-5-(2,6-dimethoxyphenyl)-1-(4-(trifluoromethoxy)benzyl)pyrrolidin-2-one as a pale yellow solid. LC-MS (conditions A): tR=0.95 min.; [M+H]+: 430.20 g/mol.

Workup

temperatureAfter cooling to rt
concentrationthe mixture was concentrated under reduced pressure before water and AcOEt
additionwere added
washThe separated organic layer was washed with brine
dry with materialdried over anh. MgSO4
filtrationfiltered
concentrationconcentrated to dryness under reduced pressure
customPurification by FC (DCM/MeOH=50/1)

Sources & evidence

ORD record: ord-c4ff4f5e366f401faa452660eecdbda0
Source dataset: uspto-grants-2016_01
DOI: 10.6084/m9.figshare.5104873.v1
Patent number: US09242970B2

Reaction notes

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