tert-Butylsulfinamide, (S)-(-)- → (NE,S)-N-[1-(5-bromo-2-fluorophenyl)-2,2-difluoroethylidene]-2-methylpropane-2-sulfinamide

HRID 876368Notes

Reaction equation

[Br:1][C:2]1[CH:3]=[CH:4][C:5]([F:13])=[C:6]([C:8](=O)[CH:9]([F:11])[F:10])[CH:7]=1.[CH3:14][C:15]([S@@:18]([NH2:20])=[O:19])([CH3:17])[CH3:16]>O1CCCC1.C(OCC)(=O)C.[O-]CC.[Ti+4].[O-]CC.[O-]CC.[O-]CC>[Br:1][C:2]1[CH:3]=[CH:4][C:5]([F:13])=[C:6](/[C:8](=[N:20]\[S@:18]([C:15]([CH3:17])([CH3:16])[CH3:14])=[O:19])/[CH:9]([F:11])[F:10])[CH:7]=1

Participants

Conditions

Temperature: 70 °C

Procedure

To a solution of 1-(5-bromo-2-fluorophenyl)-2,2-difluoroethanone (intermediate E1.1) (13.2 g, 52.2 mmol) and (S)-(−)-2-methyl-2-propanesulfinamide (6.96 g, 57.4 mmol) in tetrahydrofuran (104 ml) was added at 23° C. titanium(IV) ethoxide (21.4 g, 19.5 ml, 93.9 mmol). The yellow solution was stirred at 70° C. for 3 hours. The cooled reaction mixture was poured into ice water, diluted with ethyl acetate and filtered through a pad of Dicalite. The organic layer was separated and washed with brine and then dried over Na2SO4. Removal of the solvent in vacuum left a yellow oil (18.25 g), which was purified by silica column chromatography 200 g, SiO2 with dichloromethane/heptane 1:1 to give (S,E)-N-(1-(5-bromo-2-fluorophenyl)-2,2-difluoroethylidene)-2-methylpropane-2-sulfinamide (14.49 g, 40.7 mmol, 78.0% yield) as a yellow oil. MS (ISP): m/z=355.9 [M+H]+ and 357.9 [M+2+H]+.

Workup

customThe cooled reaction mixture
filtrationfiltered through a pad of Dicalite
customThe organic layer was separated
washwashed with brine
dry with materialdried over Na2SO4
customRemoval of the solvent in vacuum
waitleft a yellow oil (18.25 g), which
customwas purified by silica column chromatography 200 g, SiO2 with dichloromethane/heptane 1:1

Sources & evidence

ORD record: ord-7a47fff13f2a43308bd9dad9fe6e6e8e
Source dataset: uspto-grants-2015_03
DOI: 10.6084/m9.figshare.5104873.v1
Patent number: US08987255B2

Reaction notes

Loading…