Triethylamine → 3-(4-Chlorophenyl)-3-hydroxy-2-(4-nitrobenzyl)isoindolin-1-one

HRID 1916969Notes

Reaction equation

HRID 1916969 reaction equation
Cl[C:2]1([C:12]2[CH:17]=[CH:16][C:15]([Cl:18])=[CH:14][CH:13]=2)[C:10]2[C:5](=[CH:6][CH:7]=[CH:8][CH:9]=2)[C:4](=[O:11])[O:3]1.Cl.[N+:20]([C:23]1[CH:30]=[CH:29][C:26]([CH2:27][NH2:28])=[CH:25][CH:24]=1)([O-:22])=[O:21].C(N(CC)CC)C>>[Cl:18][C:15]1[CH:16]=[CH:17][C:12]([C:2]2([OH:3])[C:10]3[C:5](=[CH:6][CH:7]=[CH:8][CH:9]=3)[C:4](=[O:11])[N:28]2[CH2:27][C:26]2[CH:25]=[CH:24][C:23]([N+:20]([O-:22])=[O:21])=[CH:30][CH:29]=2)=[CH:13][CH:14]=1

Participants

4

Reactant 3

HCID 8471TriethylamineHCID 112524674-Nitrobenzylamine hydrochlorideHCID 126920383-Chloro-3-(4-chlorophenyl)-2-benzofuran-1(3H)-one

Product 1

HCID 513497043-(4-Chlorophenyl)-3-hydroxy-2-(4-nitrobenzyl)isoindolin-1-oneYield 65%

Procedure

Distilled THF (25 mL) was added to 3-chloro-3-(4-chlorophenyl)-3H-isobenzofuran-1-one (3.2 g, 11.5 mmol), 4-nitrobenzylamine hydrochloride (2.3 g, 12.6 mmol), and triethylamine (4.8 mL, 34.5 mmol). The mixture was stirred at room temperature under nitrogen for 4 h and monitored by TLC. On completion the solvent was removed under vacuum, the residue was taken up in ethyl acetate (30 mL), washed with water (3×20 mL), brine (10 mL) and dried (MgSO4). The solvent was removed under vacuum. Recrystallisation (ethyl acetate) gave 3-(4-Chlorophenyl)-3-hydroxy-2-(4-nitrobenzyl)-2,3-dihydroisoindol-1-one as a light yellow solid (2.95 g, 7.47 mmol, 65%); Rf=0.4 (40:60: EtOAc:petrol). mp 197.1-199.7° C. λmax (CH3OH)/nm 225. IR: 3215, 1676, 1517, 1395, 1341 cm1. 1H NMR: (300 MHz, d6-DMSO) δ 4.35 (d, 1H, J=16.3 Hz, N—CH2), 4.61 (d, 1H, J=16.3 Hz, N—CH2), 7.28 (m, 4H, Ar—H), 7.45 (m, 3H, Ar—H), 7.58 (m, 2H, Ar—H), 7.79 (m, 1H, Ar—H), 8.05 (m, 2H, Ar—H). 13C NMR: (75 MHz, d6-DMSO) δ 42.1, 90.5, 123.1, 123.3, 128.4, 128.7, 129.1, 129.9, 130.3, 133.2, 133.3, 138.9, 146.4, 146.5, 149.4, 167.1. LCMS (ESI+) m/z=307.2, 368.2, 377.1. Anal. Calcd. for C21H15ClN2O4: C, 63.89; H, 3.83; N, 7.10%. Found C, 63.78; H, 3.92; N, 7.12%. HRMS (EI) m/z Calcd. for C21H15ClN2O4: 394.0720. Found 394.0714.

Workup

  1. distillationDistilled THF (25 mL)
  2. customOn completion the solvent was removed under vacuum
  3. washwashed with water (3×20 mL), brine (10 mL)
  4. dry with materialdried (MgSO4)
  5. customThe solvent was removed under vacuum
  6. customRecrystallisation (ethyl acetate)

Sources & evidence

ORD record
ord-b38aa382c9494f9aa43321a7568f4c2c
Source dataset
uspto-grants-2013_12
Patent number
US08618158B2

Reaction notes

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