1,4-Dibromobenzene → (R)-N-((R)-(4-bromophenyl)(2,4-difluorophenyl)methyl)-2-methylpropane-2-sulfinamide

HRID 1525263Notes

Reaction equation

Br[C:2]1[CH:7]=[CH:6][C:5]([Br:8])=[CH:4][CH:3]=1.[Li]CCCC.[F:14][C:15]1[CH:28]=[C:27]([F:29])[CH:26]=[CH:25][C:16]=1/[CH:17]=[N:18]/[S@@:19]([C:21]([CH3:24])([CH3:23])[CH3:22])=[O:20]>C1COCC1>[Br:8][C:5]1[CH:6]=[CH:7][C:2]([C@H:17]([C:16]2[CH:25]=[CH:26][C:27]([F:29])=[CH:28][C:15]=2[F:14])[NH:18][S@@:19]([C:21]([CH3:24])([CH3:23])[CH3:22])=[O:20])=[CH:3][CH:4]=1

Participants

Conditions

Temperature: -78 °C

Procedure

1,4-dibromobenzene (9.6 g, 40.77 mmol) was dissolved in THF (150 ml) and cooled to −78° C. under nitrogen. Then n-BuLi (16.3 ml, 40.77 mmol) was added dropwise below −60° C. After addition, the mixture was stirred at −78° C. for additional 1 h and then (R,E)-N-(2,4-difluorobenzylidene)-2-methylpropane-2-sulfinamide, 20-b, (10 g, 40.77 mmol) in anhydrous THF was added dropwise below −60° C. Then the mixture was allowed to stir at room temperature for 6 h. The mixture was quenched with saturated NH4Cl followed by extraction with ethyl acetate. The organic layer was dried over sodium sulfate and concentrated under vacuum. The residue was purified by column chromatography (petroleum ether/ethyl acetate=4/1) to provide the product, 20-c, (3.6 g, 22%). HPLC indicated that the no obvious diastereomer was observed.

Workup

additionAfter addition
stirringto stir at room temperature for 6 h
customThe mixture was quenched with saturated NH4Cl
extractionfollowed by extraction with ethyl acetate
dry with materialThe organic layer was dried over sodium sulfate
concentrationconcentrated under vacuum
customThe residue was purified by column chromatography (petroleum ether/ethyl acetate=4/1)

Sources & evidence

ORD record: ord-cc59571dc43b4ee58d9a2529bab6f998
Source dataset: uspto-grants-2015_07
DOI: 10.6084/m9.figshare.5104873.v1
Patent number: US09079930B2

Reaction notes

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