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

HRID 2427741Notes

Reaction equation

Br[C:2]1[CH:3]=[C:4]2[C:8](=[C:9]([Cl:11])[CH:10]=1)[C:7](=[O:12])[N:6]([CH2:13][C:14]1[CH:19]=[CH:18][C:17]([Cl:20])=[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:56][CH:57]([F:60])[CH2:58][OH:59]>C1(C)C=CC=CC=1.C([O-])(=O)C.[Pd+2].C([O-])(=O)C>[F:56][CH:57]([F:60])[CH2:58][O:59][C:2]1[CH:3]=[C:4]2[C:8](=[C:9]([Cl:11])[CH:10]=1)[C:7](=[O:12])[N:6]([CH2:13][C:14]1[CH:19]=[CH:18][C:17]([Cl:20])=[CH:16][CH:15]=1)[CH2:5]2

Participants

Conditions

Temperature: 110 °C

Procedure

A mixture of 5-bromo-7-chloro-2-(4-chloro-benzyl)-2,3-dihydro-isoindol-1-one (0.110 g, 0.297 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 (0.163 g, 0.5 mmol) in toluene (5 mL) was treated with 2,2-difluoro ethanol (0.05 mL, 0.6 mmol) and stirred at 110° C. for 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 (0.055 g, 50%). 1H NMR (300 MHz, CDCl3): δ (ppm) 4.14-4.26 (m, 4H), 4.72 (s, 2H), 5.92-6.32 (m, 1H), 6.82 (s, 1H), 6.97 (s, 1H), 7.23-7.33 (m, 4H). GC-MS: m/z 371 (M)+, 336 (M−35)+.

Workup

customAfter this time the solvent was evaporated

Sources & evidence

ORD record: ord-30ac5cf1b0324c46a55a017425a407c8
Source dataset: uspto-grants-2011_06
DOI: 10.6084/m9.figshare.5104873.v1
Patent number: US07968570B2

Reaction notes

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