tert-Butylsulfinamide, (S)-(-)- → (S)-2-Methyl-propane-2-sulfinic acid[1-(6-bromo-3-fluoro-4-triethylsilanyl-pyridin-2-yl)-2,2-difluoro-ethylidene]-amide

HRID 538376

Reaction equation

[Br:1][C:2]1[N:7]=[C:6]([C:8](=O)[CH:9]([F:11])[F:10])[C:5]([F:13])=[C:4]([Si:14]([CH2:19][CH3:20])([CH2:17][CH3:18])[CH2:15][CH3:16])[CH:3]=1.[CH3:21][C:22]([S@@:25]([NH2:27])=[O:26])([CH3:24])[CH3:23]>C1COCC1.C(O[Ti](OCC)(OCC)OCC)C>[Br:1][C:2]1[N:7]=[C:6]([C:8](=[N:27][S@:25]([C:22]([CH3:24])([CH3:23])[CH3:21])=[O:26])[CH:9]([F:11])[F:10])[C:5]([F:13])=[C:4]([Si:14]([CH2:19][CH3:20])([CH2:17][CH3:18])[CH2:15][CH3:16])[CH:3]=1

Participants

Conditions

Temperature: 80 °C

Procedure

A mixture of 1-(6-bromo-3-fluoro-4-triethylsilanyl-pyridin-2-yl)-2,2-difluoro-ethanone (9.8 g, 26.6 mmol), (S)-2-methylpropane-2-sulfinamide (3.23 g, 26.6 mmol) and tetraethoxytitanium (13.81 ml, 53.2 mmol) in THF (66.5 ml) was stirred at 80° C. in 3 capped microwave vials (3×25 ml) for 3 hours. The cold reaction mixture was poured into ice cold water and the precipitate was filtered through a pad of hyflo and washed thoroughly with ethyl acetate. The organic phase was washed with brine, dried over sodium sulfate, filtered and evaporated. The crude product (12.5 g) was chromatographed over silica gel (cyclohexane:ethyl acetate 5:1) to afford the title compound. 7.96 g (63% yield).

Workup

customThe cold reaction mixture
additionwas poured into ice cold water
filtrationthe precipitate was filtered through a pad of hyflo
washwashed thoroughly with ethyl acetate
washThe organic phase was washed with brine
dry with materialdried over sodium sulfate
filtrationfiltered
customevaporated
customThe crude product (12.5 g) was chromatographed over silica gel (cyclohexane:ethyl acetate 5:1)

Sources & evidence

ORD record: ord-f47eed4858b84ce4beed63337abe67a1
Source dataset: uspto-grants-2014_10
DOI: 10.6084/m9.figshare.5104873.v1
Patent number: US08865712B2

Linked notes

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