Sulfuric Acid → 2-Amino-5-propionyl-4-trifluoromethyl-benzoic acid methyl ester

HRID 1894021Notes

Reaction equation

[CH3:1][O:2][C:3](=[O:22])[C:4]1[CH:9]=[C:8]([C:10](=[O:13])[CH2:11][CH3:12])[C:7]([C:14]([F:17])([F:16])[F:15])=[CH:6][C:5]=1[NH:18]C(=O)C.S(=O)(=O)(O)O>CO.O.CCOC(C)=O>[CH3:1][O:2][C:3](=[O:22])[C:4]1[CH:9]=[C:8]([C:10](=[O:13])[CH2:11][CH3:12])[C:7]([C:14]([F:16])([F:15])[F:17])=[CH:6][C:5]=1[NH2:18]

Participants

Conditions

Temperature: 60 °C

Procedure

A solution of 2-acetylamino-5-propionyl-4-trifluoromethyl-benzoic acid methyl ester (260 mg, 0.82 mmol) in MeOH (2.6 mL) and water (0.54 mL) was treated with concentrated sulfuric acid (0.26 mL) and the mixture was heated to 60° C. for 1 h. It was then allowed to cool to r.t., and diluted with EtOAc. This mixture was washed once with aqueous sodium hydrogencarbonate (pH=8), once 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 100:0→80:20) to furnish 2-amino-5-propionyl-4-trifluoromethyl-benzoic acid methyl ester (185 mg, 0.67 mmol, 82%) as a white powder, m.p. 141-144° C., ESI-MS: m/z 276 [M+H]+.

Workup

temperatureto cool to r.t.
washThis mixture was washed once with aqueous sodium hydrogencarbonate (pH=8), once 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 100:0→80:20)

Sources & evidence

ORD record: ord-e193e28465e242498a3bd047c84485b6
Source dataset: uspto-grants-2013_08
DOI: 10.6084/m9.figshare.5104873.v1
Patent number: US08513268B2

Reaction notes

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