2-Acetylamino-5-formyl-4-trifluoromethyl-benzoic acid methyl ester → 2-Acetylamino-5-(1-hydroxy-propyl)-4-trifluoromethyl-benzoic acid methyl ester

HRID 1894019Notes

Reaction equation

[CH3:1][O:2][C:3](=[O:20])[C:4]1[CH:9]=[C:8]([CH:10]=[O:11])[C:7]([C:12]([F:15])([F:14])[F:13])=[CH:6][C:5]=1[NH:16][C:17](=[O:19])[CH3:18].[CH2:21]([Mg]Br)[CH3:22]>C(OCC)C>[CH3:1][O:2][C:3](=[O:20])[C:4]1[CH:9]=[C:8]([CH:10]([OH:11])[CH2:21][CH3:22])[C:7]([C:12]([F:15])([F:14])[F:13])=[CH:6][C:5]=1[NH:16][C:17](=[O:19])[CH3:18]

Participants

Conditions

Temperature: 0 °C

Procedure

A solution of 2-acetylamino-5-formyl-4-trifluoromethyl-benzoic acid methyl ester (840 mg, 2.90 mmol) in dry diethyl ether (29 mL) was cooled to 0° C. and a solution of ethylmagnesium bromide (1M in THF, 5.8 mL, 5.8 mmol) was added dropwise. The mixture was stirred for 1 h at 0° C. and the reaction was quenched by adding aqueous ammonium chloride solution. This mixture was extracted once with EtOAc and the organic phase was then washed with brine, dried over anhydrous sodium sulfate, filtered and concentrated in vacuo. The crude product was purified by flash chromatography (silica gel 60, hexanes/EtOAc 80:20→70:30) to furnish 2-acetylamino-5-(1-hydroxy-propyl)-4-trifluoromethyl-benzoic acid methyl ester (262 mg, 0.82 mmol, 28%) as a white solid, m.p. 120-122° C., ESI-MS: m/z 320 [M+H]+.

Workup

customthe reaction was quenched
additionby adding aqueous ammonium chloride solution
extractionThis mixture was extracted once with EtOAc
washthe organic phase was then washed with brine
dry with materialdried over anhydrous sodium sulfate
filtrationfiltered
concentrationconcentrated in vacuo
customThe crude product was purified by flash chromatography (silica gel 60, hexanes/EtOAc 80:20→70:30)

Sources & evidence

ORD record: ord-79f7c2606c2a4e13b05294628dce5009
Source dataset: uspto-grants-2013_08
DOI: 10.6084/m9.figshare.5104873.v1
Patent number: US08513268B2

Reaction notes

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