1-Bromo-4-fluorobenzene → HCID 67391448, compound

HRID 907608Notes

Reaction equation

[F:1][C:2]1[CH:7]=[CH:6][C:5](Br)=[CH:4][CH:3]=1.[Li]CCCC.[Si:14]([O:21][CH2:22][C@@H:23]([N:30]=[CH:31][C:32]([F:42])([F:41])[O:33][C:34]1[CH:39]=[CH:38][C:37]([F:40])=[CH:36][CH:35]=1)[CH2:24][S:25][CH2:26][CH:27]1[CH2:29][CH2:28]1)([C:17]([CH3:20])([CH3:19])[CH3:18])([CH3:16])[CH3:15]>C1COCC1.C(OCC)C>[Si:14]([O:21][CH2:22][C@@H:23]([NH:30][C@@H:31]([C:5]1[CH:6]=[CH:7][C:2]([F:1])=[CH:3][CH:4]=1)[C:32]([F:41])([F:42])[O:33][C:34]1[CH:35]=[CH:36][C:37]([F:40])=[CH:38][CH:39]=1)[CH2:24][S:25][CH2:26][CH:27]1[CH2:28][CH2:29]1)([C:17]([CH3:20])([CH3:19])[CH3:18])([CH3:16])[CH3:15]

Participants

Conditions

Temperature: -78 °C

Procedure

To a solution of 4-fluorobromobenzene (0.589 ml, 5.36 mmol) in anhydrous THF (5 ml) at −78° C., under nitrogen, a solution of 2.5 M of BuLi in hexanes (2.1 ml, 5.36 mmol) was added. After stirring the reaction mixture for 1 h at −78° C., a solution of [2-(tert-butyldimethylsilanyloxy)-1(R)-cyclopropylmethylsulfanylmethylethyl]-[2,2-difluoro-2-(4-fluorophenoxy)ethylidene]amine (0.8 g, 1.78 mmol) in THF (5 ml) was added. After stirring for 2 h at −40° C., the reaction mixture was diluted with ethyl ether and the solution was washed with 10% ammonium chloride solution, brine and dried over sodium sulfate. Concentration under vacuum followed by column chromatography over silica gel with ethyl acetate/hexanes (1/10) gave [2-(tert-butyldimethylsilanyloxy)-1(R)-cyclopropylmethylsulfanylmethylethyl]-[2,2-difluoro-2-(4-fluorophenoxy)-1(S)-(4-fluorophenyl)-ethyl]amine (0.75 g, 77%) as an oil.

Workup

stirringAfter stirring for 2 h at −40° C.
washthe solution was washed with 10% ammonium chloride solution, brine
dry with materialdried over sodium sulfate
concentrationConcentration under vacuum

Sources & evidence

ORD record: ord-bdcda6aafd5f4a7bb2be9866d726d9c5
Source dataset: uspto-grants-2011_09
DOI: 10.6084/m9.figshare.5104873.v1
Patent number: US08013186B2

Reaction notes

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