Trifluoroacetic acid → 1-(4-Fluorophenyl)cyclopropanecarboxamide
Reaction equation
COC1C=C(OC)C=CC=1C[NH:6][C:7]([C:9]1([C:12]2[CH:17]=[CH:16][C:15]([F:18])=[CH:14][CH:13]=2)[CH2:11][CH2:10]1)=[O:8].C(O)(C(F)(F)F)=O>>[F:18][C:15]1[CH:14]=[CH:13][C:12]([C:9]2([C:7]([NH2:6])=[O:8])[CH2:11][CH2:10]2)=[CH:17][CH:16]=1Participants
Procedure
A mixture of N-(2,4-dimethoxybenzyl)-1-(4-fluorophenyl)cyclopropanecarboxamide (1.5 g, 4.55 mmol) and TFA (7.02 mL, 91 mmol) was stirred at rt for 2 h. The reaction mixture was concentrated under vacuum. The residue was suspended in EtOAc (20 mL) and sat'd aqueous sodium bicarbonate (20 mL). The suspension was filtered and the filter cake was washed with EtOAc. The EtOAc layer of the filtrate was separated and the aqueous layer was extracted with ethyl acetae (2×10 mL). The combined EtOAc layers layers were washed with aqueous sodium bicarbonate and brine, dried over magnesium sulfate, and concentrated. The residue was triturated with a minimum amount of MeOH to give 1-(4-fluorophenyl)cyclopropanecarboxamide (0.7 g, 3.71 mmol, 81% yield) as white solid. 1H NMR (400 MHz, CHLOROFORM-d) δ 7.48-7.37 (m, 2H), 7.12-7.02 (m, 2H), 5.70 (br. s., 1H), 5.28 (br. s., 1H), 1.63 (q, J=3.8 Hz, 2H), 1.07 (q, J=3.8 Hz, 2H). LCMS: M+1=180.0.
Workup
- concentrationThe reaction mixture was concentrated under vacuum
- filtrationThe suspension was filtered
- washthe filter cake was washed with EtOAc
- customThe EtOAc layer of the filtrate was separated
- extractionthe aqueous layer was extracted with ethyl acetae (2×10 mL)
- washThe combined EtOAc layers layers were washed with aqueous sodium bicarbonate and brine
- dry with materialdried over magnesium sulfate
- concentrationconcentrated
- customThe residue was triturated with a minimum amount of MeOH
Sources & evidence
- ORD record
- ord-fdf9eae0c5324f68860f2217122a11b1
- Source dataset
- uspto-grants-2014_07
- Patent number
- US08765767B2
Reaction notes
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