(4-Chlorophenyl)acetic acid → 1-[5-Bromo-2,3-difluoro-4-(trimethylsilyl)phenyl]-2-(4-chlorophenyl)ethanone
Reaction equation
C[Si]([N-][Si](C)(C)C)(C)C.[Na+].[Cl:11][C:12]1[CH:17]=[CH:16][C:15]([CH2:18][C:19]([OH:21])=O)=[CH:14][CH:13]=1.[Br:22][C:23]1[C:24]([Si:35]([CH3:38])([CH3:37])[CH3:36])=[C:25]([F:34])[C:26]([F:33])=[C:27]([CH:32]=1)C(OC)=O>C1COCC1.Cl>[Br:22][C:23]1[C:24]([Si:35]([CH3:38])([CH3:37])[CH3:36])=[C:25]([F:34])[C:26]([F:33])=[C:27]([C:19](=[O:21])[CH2:18][C:15]2[CH:14]=[CH:13][C:12]([Cl:11])=[CH:17][CH:16]=2)[CH:32]=1Participants
Reactant 3
Product 1
Reagents, catalysts & solvents 2
Procedure
To a solution of NaHMDS (1.0 M in THF, 7.7 mL, 7.7 mmol) in anhydrous THF (25 mL) at −78° C. was added a solution of 4-chlorophenylacetic acid (0.528 g, 3.09 mmol) in anhydrous THF (25 mL) over 10 minutes. The solution was stirred for 5 minutes, then a solution of the product of Step C (4.16 g, 7.8 mmol) in THF (25 mL) was added drop wise over 10 minutes. The mixture was stirred at −78° C. for two hours. The mixture was diluted with 2N HCl (aq, 50 mL), then the product was extracted into EtOAc. The organics were dried over Na2SO4, filtered, then concentrated. The resulting residue was purified by silica gel chromatography eluting with 0-50% toluene/hexanes to afford the title compound. 1H NMR (600 MHz, CDCl3): δ 7.74 (dd, J=5.3, 1.8 Hz, 1H); 7.31 (d, J=8.2 Hz, 2H); 7.16 (d, J=8.5 Hz, 2H); 4.22 (s, 2H); 0.48 (s, 9H).
Workup
- stirringThe mixture was stirred at −78° C. for two hours
- extractionthe product was extracted into EtOAc
- dry with materialThe organics were dried over Na2SO4
- filtrationfiltered
- concentrationconcentrated
- customThe resulting residue was purified by silica gel chromatography
- washeluting with 0-50% toluene/hexanes
Sources & evidence
- ORD record
- ord-6eb1d8250863439a848c0c51531978a4
- Source dataset
- uspto-grants-2012_11
- Patent number
- US08318667B2
Reaction notes
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