Methyl chlorodifluoroacetate → 5-Fluoro-7-trifluoromethyl-2-(4-trifluoromethoxy-benzyl)-2,3-dihydro-isoindol-1-one

HRID 2427687Notes

Reaction equation

[F-:1].[K+].[F:3][C:4]1[CH:5]=[C:6]2[C:10](=[C:11](I)[CH:12]=1)[C:9](=[O:14])[N:8]([CH2:15][C:16]1[CH:21]=[CH:20][C:19]([O:22][C:23]([F:26])([F:25])[F:24])=[CH:18][CH:17]=1)[CH2:7]2.COC(=O)[C:30](Cl)([F:32])[F:31]>CN(C=O)C.[Cu]I>[F:3][C:4]1[CH:5]=[C:6]2[C:10](=[C:11]([C:30]([F:32])([F:1])[F:31])[CH:12]=1)[C:9](=[O:14])[N:8]([CH2:15][C:16]1[CH:21]=[CH:20][C:19]([O:22][C:23]([F:26])([F:25])[F:24])=[CH:18][CH:17]=1)[CH2:7]2

Participants

Conditions

Temperature: 140 °C

Procedure

CuI (0.129 g, 0.68 mmol) and potassium fluoride (0.039 g, 0.68 mmol) were added under an N2 atmosphere to a solution 5-fluoro-7-iodo-2-(4-trifluoromethoxy-benzyl)-2,3-dihydro-isoindol-1-one (0.260 g, 0.58 mmol) and chloro-difluoro-acetic acid methyl ester (0.072 mL, 0.098 mmol) in DMF (4 mL). The mixture was stirred at 140° C. for 18 h. The reaction was cooled and the solvent evaporated. Silica gel column chromatography using 30% ethyl acetate in hexane afforded 5-fluoro-7-trifluoromethyl-2-(4-trifluoromethoxy-benzyl)-2,3-dihydro-isoindol-1-one (0.070 g, 31%). 1H NMR (300 MHz, CDCl3): δ (ppm) 4.41 (s, 2H), 4.85 (s, 2H) 7.23-7.58 (m, 6H).

Workup

temperatureThe reaction was cooled
customthe solvent evaporated

Sources & evidence

ORD record: ord-af8f134200804f229c44546069b0a286
Source dataset: uspto-grants-2011_06
DOI: 10.6084/m9.figshare.5104873.v1
Patent number: US07968570B2

Reaction notes

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