Pyridine → (R)-4-(5-bromo-2-fluoro-phenyl)-3-(2,4-dimethoxy-benzyl)-4-methyl-[1,2,3]oxathiazolidine 2-oxide

HRID 920144Notes

Reaction equation

[Br:1][C:2]1[CH:3]=[CH:4][C:5]([F:24])=[C:6]([C@:8]([NH:12][CH2:13][C:14]2[CH:19]=[CH:18][C:17]([O:20][CH3:21])=[CH:16][C:15]=2[O:22][CH3:23])([CH3:11])[CH2:9][OH:10])[CH:7]=1.N1C=CC=CC=1.[S:31](Cl)(Cl)=[O:32]>ClCCl>[Br:1][C:2]1[CH:3]=[CH:4][C:5]([F:24])=[C:6]([C:8]2([CH3:11])[CH2:9][O:10][S@@:31](=[O:32])[N:12]2[CH2:13][C:14]2[CH:19]=[CH:18][C:17]([O:20][CH3:21])=[CH:16][C:15]=2[O:22][CH3:23])[CH:7]=1

Participants

Conditions

Temperature: 23 °C

Procedure

To a solution of (R)-2-(5-bromo-2-fluorophenyl)-2-(2,4-dimethoxybenzylamino)propan-1-ol (14.1 g, 35.4 mmol, Eq: 1.00) and pyridine (14.0 g, 14.3 ml, 177 mmol, Eq: 5.0) in dichloromethane (258 ml) at 78° C. was dropwise added thionyl chloride (5.05 g, 3.1 ml, 42.5 mmol, Eq: 1.2), stirring was continued at 78° C. for 5 min, the cooling bath was removed and the mixture was slowly warmed up to 23° C. and stirring was continued for 20 min. Extracted with 5% citric acid and sat NaHCO3-sol., dried the organic layer over Na2SO4, filtered off and evaporated totally to give the (R)-4-(5-bromo-2-fluoro-phenyl)-3-(2,4-dimethoxy-benzyl)-4-methyl-[1,2,3]oxathiazolidine 2-oxide (15.7 g, 35.3 mmol, 99.8% yield) as a light yellow oil, which needed no further purification. MS (ISP): m/z=444.1 [M+H]+ and 446.0 [M+2+H]+.

Workup

customat 78° C.
customthe cooling bath was removed
stirringstirring
waitwas continued for 20 min
extractionExtracted with 5% citric acid
dry with material, dried the organic layer over Na2SO4
filtrationfiltered off
customevaporated totally

Sources & evidence

ORD record: ord-d49ba2b98a8742f1ae2799992729067a
Source dataset: uspto-grants-2016_03
DOI: 10.6084/m9.figshare.5104873.v1
Patent number: US09273042B2

Reaction notes

Loading…