Cesium carbonate → 5-(2,2-Difluoro-ethoxy)-7-methyl-2-(4-trifluoromethoxy-benzyl)-2,3-dihydro-isoindol-1-one

HRID 2427739Notes

Reaction equation

Br[C:2]1[CH:3]=[C:4]2[C:8](=[C:9]([CH3:11])[CH:10]=1)[C:7](=[O:12])[N:6]([CH2:13][C:14]1[CH:19]=[CH:18][C:17]([O:20][C:21]([F:24])([F:23])[F:22])=[CH:16][CH:15]=1)[CH2:5]2.C(P(C(C)(C)C)C1C=CC2C(=CC=CC=2)C=1C1C2C(=CC=CC=2)C=CC=1)(C)(C)C.C(=O)([O-])[O-].[Cs+].[Cs+].[F:60][CH:61]([F:64])[CH2:62][OH:63]>C1(C)C=CC=CC=1.C([O-])(=O)C.[Pd+2].C([O-])(=O)C>[F:60][CH:61]([F:64])[CH2:62][O:63][C:2]1[CH:3]=[C:4]2[C:8](=[C:9]([CH3:11])[CH:10]=1)[C:7](=[O:12])[N:6]([CH2:13][C:14]1[CH:19]=[CH:18][C:17]([O:20][C:21]([F:24])([F:23])[F:22])=[CH:16][CH:15]=1)[CH2:5]2

Participants

Conditions

Temperature: 110 °C

Procedure

A mixture of 5-bromo-7-methyl-2-(4-trifluoromethoxy-benzyl)-2,3-dihydro-isoindol-1-one (0.400 g, 1 mmol), palladium(II) acetate (0.004 g, 0.02 mmol), rac-2-(di-t-butylphosphino)-1,1′-binaphthyl (0.009 g, 0.025 mmol), and cesium carbonate (0.488 g, 1.5 mmol) in toluene (5 mL) was treated with 2,2-difluoro ethanol (0.164 mL, 2 mmol) and stirred at 110° C. for 8-12 h. After this time the solvent was evaporated and silica gel column chromatography using, typically 30% ethyl acetate in hexane, afforded the desired product (0.082 g, 20%). 1H NMR (300 MHz, CDCl3): δ (ppm) 2.74 (s, 3H), 4.22 (m, 4H), 4.73 (s, 2H), 5.94-6.32 (m, 1), 6.75 (d, 2H), 7.18 (d, 2H), 7.35 (d, 2H). GC-MS: m/z 401 (M)+, 316 (M−85)+.

Workup

customAfter this time the solvent was evaporated

Sources & evidence

ORD record: ord-6606c07a33d241dfaf94b7c772022660
Source dataset: uspto-grants-2011_06
DOI: 10.6084/m9.figshare.5104873.v1
Patent number: US07968570B2

Reaction notes

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