N-Methoxy-N-methyl-2-(2,3,5-trifluorophenyl)acetamide → 1-(2,3,5-Trifluorophenyl)propan-2-one

HRID 706388Notes

Reaction equation

[CH3:1][Mg]Cl.CON(C)[C:7](=[O:18])[CH2:8][C:9]1[CH:14]=[C:13]([F:15])[CH:12]=[C:11]([F:16])[C:10]=1[F:17]>C1COCC1>[F:17][C:10]1[C:11]([F:16])=[CH:12][C:13]([F:15])=[CH:14][C:9]=1[CH2:8][C:7](=[O:18])[CH3:1]

Participants

Conditions

Temperature: 47.5 °C

Procedure

A solution of CeCl3 (11.44 g, 0.045 mol) in THF (350 mL) was degassed for 1 h and heated to 45-50° C. for 5 h. When the solution was cooled to −10-5° C., MeMgCl (19.44 g, 0.26 mol) in THF was added and the mixture was stirred for 1 h at −10-5° C. After amide 43 (30.3 g, 0.13 mol) was charged into the reaction mixture at −10-5° C., the mixture was stirred for 5 h at 10-20° C. After the reaction was complete, the mixture was quenched by 1M HCl, and then partitioned with water and EtOAc. The organic phase was dried over Na2SO4 and concentrated. The crude residual was further purified by flash chromatography on silica gel (2-10% EtOAc/PE) to give 44 (20.8 g, 85% yield). 1H NMR (CDCl3, 400 MHz): δ 6.91-6.78 (m, 1H), 6.69 (dd, 1H), 3.77 (d, 2H), 2.25 (s, 3H); MS (ESI) m/e [M+H]+: 189.05.

Workup

temperatureWhen the solution was cooled to −10-5° C.
stirringthe mixture was stirred for 5 h at 10-20° C
customthe mixture was quenched by 1M HCl
custompartitioned with water and EtOAc
dry with materialThe organic phase was dried over Na2SO4
concentrationconcentrated
customThe crude residual was further purified by flash chromatography on silica gel (2-10% EtOAc/PE)

Sources & evidence

ORD record: ord-f8e8e89dc2444a0abc36b5775342f180
Source dataset: uspto-grants-2015_11
DOI: 10.6084/m9.figshare.5104873.v1
Patent number: US09174989B2

Reaction notes

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