Ethyl Acetate → 7-Chloro-2-[1-(4-phenoxyphenyl)-ethyl]-2,3-dihydroisoindol-1-one

HRID 2427561Notes

Reaction equation

HRID 2427561 reaction equation
[O:1]([C:8]1[CH:13]=[CH:12][C:11]([CH:14]([NH2:16])[CH3:15])=[CH:10][CH:9]=1)[C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][CH:3]=1.C[O:18][C:19](=O)[C:20]1[C:25]([Cl:26])=[CH:24][CH:23]=[CH:22][C:21]=1[CH2:27]Br.C([O-])([O-])=O.[K+].[K+].C(OCC)(=O)C>C1(C)C=CC=CC=1>[Cl:26][C:25]1[CH:24]=[CH:23][CH:22]=[C:21]2[C:20]=1[C:19](=[O:18])[N:16]([CH:14]([C:11]1[CH:10]=[CH:9][C:8]([O:1][C:2]3[CH:7]=[CH:6][CH:5]=[CH:4][CH:3]=3)=[CH:13][CH:12]=1)[CH3:15])[CH2:27]2

Participants

6

Reactant 4

HCID 8857Ethyl AcetateHCID 11430Potassium CarbonateHCID 592071-(4-Phenoxyphenyl)ethan-1-amineHCID 22935208Methyl 2-(bromomethyl)-6-chlorobenzoate

Product 1

HCID 116030087-Chloro-2-[1-(4-phenoxyphenyl)-ethyl]-2,3-dihydroisoindol-1-oneYield 34%

Reagents, catalysts & solvents 1

HCID 1140TolueneSolvent

Procedure

A mixture of 1-(4-phenoxyphenyl)ethylamine (121 mg, 0.57 mmol), 2-bromomethyl-6-chloro-benzoic acid methyl ester (150 mg, 0.57 mmol), and K2CO3 (1 g, 7.2 mmol) in toluene (10 mL) was heated at reflux with stirring for 16 h. Workup and silica gel column chromatography using a gradient of hexanes to 30% ethyl acetate in hexanes afforded 7-chloro-2-[1-(4-phenoxyphenyl)-ethyl]-2,3-dihydroisoindol-1-one (70 mg, 34%). GC/MS gave: m/z (rel.int.) 365 (M+, 9), 363 (M+23), 350 (25), 348 (63), 211 (32), 196 (65), 168 (33), 152 (54), 141 (27), 124 (27), 115 (27), 89 (35), and 77 (100). 1H NMR (300 MHz, CDCl3): δ 1.68 (d, 3H), 3.99 (d, 1H), 4.15 (d, 1H), 5.79 (q, 1H), 6.98 (br t, 4H), 7.13 (t, 1H), 7.26-7.10 (br m, 7H).

Workup

  1. temperaturewas heated
  2. temperatureat reflux

Sources & evidence

ORD record
ord-311a6bd7a0d341a2b1af38b86c267678
Source dataset
uspto-grants-2011_06
Patent number
US07968570B2

Reaction notes

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