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

HRID 906522Notes

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]Cl)[CH2:22][CH3:23]>CCOCC>[CH3:1][O:2][C:3](=[O:20])[C:4]1[CH:9]=[C:8]([CH:10]([OH:11])[CH2:21][CH2:22][CH3:23])[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: 20 °C

Procedure

To a solution of 2-acetylamino-5-formyl-4-trifluoromethyl-benzoic acid methyl ester (1.52 g, 5.26 mmol) in absolute Et2O (52 mL), under argon, was added a solution of propylmagnesium chloride (2.0 M in Et2O, 5.3 mL, 11 mmol) over 5 min at 20° C. An immediate crystallisation occurred along with an exotherm. The reaction mixture was cooled to 20° C. using an ice/water bath. The reaction mixture was stirred at r.t. for 1 h then poured onto sat. aq NH4Cl and EtOAc. The pH was adjusted to 7 with sat. aq NH4Cl and the layers were separated. The organic phase was washed with brine, dried (Na2SO4), filtered and concentrated in vacuo. The residue was purified by flash column chromatography (25 g silica gel, hexanes/EtOAc (1:0→7:3)) to give product as colorless crystals (409 mg, 23%). m.p.: 97-101° C., ESI-MS: m/z 334 [M+H]+, m/z 332 [M−H]−.

Workup

customAn immediate crystallisation
additionthen poured onto sat. aq NH4Cl and EtOAc
customthe layers were separated
washThe organic phase was washed with brine
dry with materialdried (Na2SO4)
filtrationfiltered
concentrationconcentrated in vacuo
customThe residue was purified by flash column chromatography (25 g silica gel, hexanes/EtOAc (1:0→7:3))

Sources & evidence

ORD record: ord-434d815660814351b0effdc8c7c09ab0
Source dataset: uspto-grants-2011_09
DOI: 10.6084/m9.figshare.5104873.v1
Patent number: US08012988B2

Reaction notes

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