Lithium Hexamethyldisilazide → 1-(4-Chlorobenzo[b]thiophen-2-yl)-3-(3,5-dichlorophenyl)-4,4,4-trifluoro-3-hydroxybutan-1-one

HRID 336998Notes

Reaction equation

[Li+].C[Si]([N-][Si](C)(C)C)(C)C.[Cl:11][C:12]1[C:20]2[CH:19]=[C:18]([C:21](=[O:23])[CH3:22])[S:17][C:16]=2[CH:15]=[CH:14][CH:13]=1.[Cl:24][C:25]1[CH:26]=[C:27]([C:32](=[O:37])[C:33]([F:36])([F:35])[F:34])[CH:28]=[C:29]([Cl:31])[CH:30]=1>C1COCC1>[Cl:11][C:12]1[C:20]2[CH:19]=[C:18]([C:21](=[O:23])[CH2:22][C:32]([C:27]3[CH:28]=[C:29]([Cl:31])[CH:30]=[C:25]([Cl:24])[CH:26]=3)([OH:37])[C:33]([F:36])([F:35])[F:34])[S:17][C:16]=2[CH:15]=[CH:14][CH:13]=1

Participants

Conditions

Temperature: -78 °C

Procedure

Add a solution of LiHMDS (1 M in THF, 4.3 ml, 4.31 mmol) to a mixture of 1-(4-chlorobenzo[b]thiophen-2-yl)ethanone (0.6 g, 2.87 mmol) in dry THF (10 mL) at −78° C. under N2. After stirring 1.5 hour at −78° C., add 1-(3,5-dichlorophenyl)-2,2,2-trifluoroethanone (836 mg, 3.44 mmol) to the reaction mixture and stir the resultant mixture for additional 2 hours. Quench the reaction with saturated NH4Cl solution and extract the aqueous mixture with EtOAc (10 mL×3). The combined organic layers are washed with brine, dried over anhydrous Na2SO4 and concentrated under vacuum afford crude 1-(4-chlorobenzo[b]thiophen-2-yl)-3-(3,5-dichlorophenyl)-4,4,4-trifluoro-3-hydroxybutan-1-one as brown solid (1.1 g, 84.6%). 1H NMR (400 MHz, CDCl3) δ 8.10-8.07 (s, 1H), 7.75 (d, J=5.2, 1H), 7.47-7.36 (m, 2H), 2.72-2.68 (s, 3H).

Workup

customQuench
customthe reaction with saturated NH4Cl solution
extractionextract the aqueous mixture with EtOAc (10 mL×3)
washThe combined organic layers are washed with brine
dry with materialdried over anhydrous Na2SO4
concentrationconcentrated under vacuum

Sources & evidence

ORD record: ord-816605c80f2246a99951bec46124edd9
Source dataset: uspto-grants-2014_11
DOI: 10.6084/m9.figshare.5104873.v1
Patent number: US08889710B2

Reaction notes

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