Ethyl Acetate → 5-(2,2-Difluoro-ethoxy)-7-methoxy-2-(4-trifluoromethoxy-benzyl)-2,3-dihydro-isoindol-1-one

HRID 2427748Notes

Reaction equation

HRID 2427748 reaction equation
Cl[C:2]1[CH:3]=[C:4]([O:24][CH2:25][CH:26]([F:28])[F:27])[CH:5]=[C:6]2[C:10]=1[C:9](=[O:11])[N:8]([CH2:12][C:13]1[CH:18]=[CH:17][C:16]([O:19][C:20]([F:23])([F:22])[F:21])=[CH:15][CH:14]=1)[CH2:7]2.C[O-].[Na+].CO.[C:34](OCC)(=[O:36])C>CO.CCCCCC>[F:28][CH:26]([F:27])[CH2:25][O:24][C:4]1[CH:5]=[C:6]2[C:10](=[C:2]([O:36][CH3:34])[CH:3]=1)[C:9](=[O:11])[N:8]([CH2:12][C:13]1[CH:18]=[CH:17][C:16]([O:19][C:20]([F:22])([F:21])[F:23])=[CH:15][CH:14]=1)[CH2:7]2

Participants

6

Reactant 3

HCID 8857Ethyl AcetateHCID 23694274Sodium methanolate methanolHCID 866356765-(2,2-Difluoro-ethoxy)-7-chloro-2-(4-trifluoromethoxy-benzyl)-2,3-dihydro-isoindol-1-one

Product 1

HCID 866356785-(2,2-Difluoro-ethoxy)-7-methoxy-2-(4-trifluoromethoxy-benzyl)-2,3-dihydro-isoindol-1-oneYield 51%

Reagents, catalysts & solvents 2

HCID 887MethanolSolventHCID 8058HexaneSolvent

Conditions

Temperature
100 °C

Procedure

A mixture of 7-chloro-5-(2,2-Difluoro-ethoxy)-2-(4-trifluoromethoxy-benzyl)-2,3-dihydro-isoindol-1-one (0.057 g, 0.14 mmol), and 30% sodium methoxide-methanol (0.12 mL) in methanol (4 mL) was stirred at 100° C. for 1 h. Workup and silica gel column chromatography using 30% ethyl acetate in hexane afforded 5-(2,2-Difluoro-ethoxy)-7-methoxy-2-(4-trifluoromethoxy-benzyl)-2,3-dihydro-isoindol-1-one (0.030 g, 51%). 1H NMR (300 MHz, CDCl3): δ (ppm) 3.96 (s, 3H), 4.22 (m, 4H), 4.73 (s, 2H), 5.94-6.32 (m, 1H), 6.45 (d, 2H), 7.17 (d, 2H), 7.35 (d, 2H). GC-MS: m/z 417 (M)+, 399 (M−18)+.

Sources & evidence

ORD record
ord-e9d29baeaaed4db79bc5919ce91c8360
Source dataset
uspto-grants-2011_06
Patent number
US07968570B2

Reaction notes

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