Ethyl Acetate → 5,7-Dichloro-2-(4-difluoromethoxy-benzyl)-2,3-dihydro-isoindol-1-one

HRID 2427752Notes

Reaction equation

HRID 2427752 reaction equation
CO[C:3](=[O:14])[C:4]1[C:9]([Cl:10])=[CH:8][C:7]([Cl:11])=[CH:6][C:5]=1[CH2:12]Br.[F:15][CH:16]([F:26])[O:17][C:18]1[CH:25]=[CH:24][C:21]([CH2:22][NH2:23])=[CH:20][CH:19]=1.C([O-])([O-])=O.[K+].[K+].C(OCC)(=O)C>C1(C)C=CC=CC=1.CCCCCC>[Cl:11][C:7]1[CH:6]=[C:5]2[C:4](=[C:9]([Cl:10])[CH:8]=1)[C:3](=[O:14])[N:23]([CH2:22][C:21]1[CH:20]=[CH:19][C:18]([O:17][CH:16]([F:15])[F:26])=[CH:25][CH:24]=1)[CH2:12]2

Participants

7

Reactant 4

HCID 8857Ethyl AcetateHCID 11430Potassium CarbonateHCID 20633524-(Difluoromethoxy)benzylamineHCID 579493492-Bromomethyl-4,6-dichlorobenzoic acid methyl ester

Product 1

HCID 579493505,7-Dichloro-2-(4-difluoromethoxy-benzyl)-2,3-dihydro-isoindol-1-oneYield 20.1%

Reagents, catalysts & solvents 2

HCID 1140TolueneSolventHCID 8058HexaneSolvent

Conditions

Temperature
100 °C

Procedure

A mixture of 2-Bromomethyl-4,6-dichloro-benzoic acid methyl ester (0.150 g, 0.5 mmol), 4-difluoromethoxy-benzyl amine (0.101 g, 0.6 mmol), and K2CO3 (0.138 g, 1.0 mmol) in toluene (4 mL) was heated with stirring at 100° C. for 2 h. Workup and silica gel column chromatography of the product using 30% ethyl acetate in hexane afforded 5,7-dichloro-2-(4-difluoromethoxy-benzyl)-2,3-dihydro-isoindol-1-one (0.036 g, 20%). 1H NMR (300 MHz, CDCl3): δ (ppm) 4.22 (s, 2H), 4.74 (s, 214), 6.49 (t, 1H) 7.11 (d, 2H), 7.26-7.32 (m, 3H), 7.42 (s, 1H). GC-MS: m/z 357 (M)+.

Workup

  1. temperaturewas heated

Sources & evidence

ORD record
ord-62c023fbf5584827bccbb4da5851e028
Source dataset
uspto-grants-2011_06
Patent number
US07968570B2

Reaction notes

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