Methyl iodide → 2,2,2-trifluoro-N-methyl-N-[(3-nitrophenyl)methyl]acetamide

HRID 1159989Notes

Reaction equation

[H-].[Na+].[F:3][C:4]([F:19])([F:18])[C:5]([NH:7][CH2:8][C:9]1[CH:14]=[CH:13][CH:12]=[C:11]([N+:15]([O-:17])=[O:16])[CH:10]=1)=[O:6].[CH3:20]I>O1CCCC1>[F:3][C:4]([F:18])([F:19])[C:5]([N:7]([CH3:20])[CH2:8][C:9]1[CH:14]=[CH:13][CH:12]=[C:11]([N+:15]([O-:17])=[O:16])[CH:10]=1)=[O:6]

Participants

Conditions

Temperature: 0 °C

Procedure

To a suspension of a 60% dispersion of sodium hydride in mineral oil (96 mg, 2.4 mmol) in dry tetrahydrofuran (5 mL), cooled to 0° C., was added a solution of 2,2,2-trifluoro-N-[(3-nitrophenyl)methyl]acetamide (500 mg, 2.0 mmol) in 5 mL dry teterahydrofuran. After stirring for 1 hour at 0° C., methyl iodide (132 μL, 2.2 mmol) was added in one portion. The reaction was stirred for 1 hour at 0° C., and warmed to rt overnight. After 16 h, the reaction mixture was concentrated, and the residue was partitioned between saturated aqueous NaHCO3 and EtOAc. The organic layer was dried over Na2SO4, filtered, adsorbed onto silica, and purified by column chromatography to yield the desired compound (0.36 g, 1.4 mmol, 69% yield). 1H NMR (400 MHz, CDCl3): δ 8.13-8.22 (m, 2H), 7.56-7.64 (m, 2H), 4.74 (s, 2H), 3.14 (s, 3H). MS (ESI) m/z=263 [M+H]+.

Workup

customdry teterahydrofuran
stirringThe reaction was stirred for 1 hour at 0° C.
temperaturewarmed to rt overnight
waitAfter 16 h
concentrationthe reaction mixture was concentrated
customthe residue was partitioned between saturated aqueous NaHCO3 and EtOAc
dry with materialThe organic layer was dried over Na2SO4
filtrationfiltered
custompurified by column chromatography

Sources & evidence

ORD record: ord-5a6510192c7b4bc9a8a9fff92d5434c3
Source dataset: uspto-grants-2010_10
DOI: 10.6084/m9.figshare.5104873.v1
Patent number: US07812022B2

Reaction notes

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