2,5-Dimethoxybenzoyl chloride → Methyl 3-(2,5-dimethoxyphenyl)-2-(3-methoxy-4-(trifluoromethyl)phenyl)-3-oxopropanoate

HRID 2368945

Reaction equation

[CH3:1][O:2][C:3]1[CH:4]=[C:5]([CH2:13][C:14]([O:16][CH3:17])=[O:15])[CH:6]=[CH:7][C:8]=1[C:9]([F:12])([F:11])[F:10].[Li+].C[Si]([N-][Si](C)(C)C)(C)C.[CH3:28][O:29][C:30]1[CH:38]=[CH:37][C:36]([O:39][CH3:40])=[CH:35][C:31]=1[C:32](Cl)=[O:33]>C1COCC1>[CH3:28][O:29][C:30]1[CH:38]=[CH:37][C:36]([O:39][CH3:40])=[CH:35][C:31]=1[C:32](=[O:33])[CH:13]([C:5]1[CH:6]=[CH:7][C:8]([C:9]([F:11])([F:10])[F:12])=[C:3]([O:2][CH3:1])[CH:4]=1)[C:14]([O:16][CH3:17])=[O:15]

Participants

Conditions

Temperature: -78 °C

Procedure

To a solution of methyl 2-(3-methoxy-4-(trifluoromethyl)phenyl)acetate (18.6 g, 75 mmol) in anhydrous THF (250 mL) at −78° C., LiHMDS (1.0 M in THF, 79 mL, 79 mmol) was added dropwise under N2. The resulting mixture was stirred at −78° C. for 30 minutes, and a solution of 2,5-dimethoxybenzoyl chloride (15.9 g, 78 mmol; intermediate in Intermediate 1) in anhydrous THF (50 mL) was added dropwise. The reaction mixture was stirred for another 1 h at −78° C., quenched with saturated aqueous NH4Cl (100 mL), and extracted with ethyl acetate (2×100 mL). The combined organic layers were dried over anhydrous sodium sulfate and concentrated under vacuum to give the title compound (30.1 g). 1H NMR (DMSO-d6): δ 7.50 (d, 1H), 7.34 (d, 1H), 7.09-7.07 (m, 1H), 6.94-6.87 (m, 3H), 5.71 (s, 1H), 3.92 (s, 3H), 3.85 (s, 3H), 3.77 (s, 3H), 3.65 (s, 3H).

Workup

stirringThe reaction mixture was stirred for another 1 h at −78° C.
customquenched with saturated aqueous NH4Cl (100 mL)
extractionextracted with ethyl acetate (2×100 mL)
dry with materialThe combined organic layers were dried over anhydrous sodium sulfate
concentrationconcentrated under vacuum

Sources & evidence

ORD record: ord-d63be15e53e44fd49f152276629b2da4
Source dataset: uspto-grants-2014_04
DOI: 10.6084/m9.figshare.5104873.v1
Patent number: US08703810B2

Linked notes

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