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

HRID 2199284Notes

Reaction equation

HRID 2199284 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.C(N(CC)CC)C.[CH3:26][C:27]1[CH:34]=[CH:33][C:30]([CH2:31][NH2:32])=[CH:29][CH:28]=1>>[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:32]2[CH2:31][C:30]2[CH:33]=[CH:34][C:27]([CH3:26])=[CH:28][CH:29]=2)=[CH:13][CH:14]=1

Participants

4

Reactant 3

HCID 8471TriethylamineHCID 660354-MethylbenzylamineHCID 126920383-Chloro-3-(4-chlorophenyl)-2-benzofuran-1(3H)-one

Product 1

HCID 513497003-(4-Chlorophenyl)-3-hydroxy-2-(4-methylbenzyl)isoindolin-1-oneYield 81%

Procedure

Distilled THF (25 mL) was added to 3-chloro-3-(4-chlorophenyl)-3H-isobenzofuran-1-one (1.071 g, 3.84 mmol) followed by triethylamine (855.1.1 mg, 8.45 mmol, 1.178 mL) and para-methylbenzylamine (465.3 mg, 3.84 mmol, 0.489 mL) resulting in the formation of a bright yellow precipitate. The mixture was stirred at room temperature under nitrogen for 4 hours and monitored by TLC. Upon completion the mixture was then extracted with EtOAc (15 mL) and washed with saturated sodium bicarbonate (3×10 mL), water (3×10 mL) and dried (Na2SO4). Recrystallisation of the cream/yellow residue from a minimum amount of boiling ethyl acetate and excess petrol yielded the title product as a fine pale yellow crystalline solid (1.090 g, 3.10 mmol, 81%). 1H NMR: (300 MHz, DMSO) δ ppm 2.21 (s, 3H, HO, 4.20 (d, 1H, J=15.62 Hz, H9), 4.40 (d, 1H, J=15.36 Hz, H9′), 6.95 (d, 2H J=7.97 Hz, H11, H13), 7.04 (d, 2H J=8.00 Hz, H10-H14) 7.27 (m, 5H, H1-H5), 7.55 (m, 2H, H6-H7) 7.74 (d, 1H, H8). 13C NMR: (75 Hz, DMSO) δ 20.90 (CH3), 42.53 (N—CH2), 90.57 (O—C—N), 122.89, 123.15, 128.36, 128.38, 128.61, 129.66, 130.85, 132.91, 133.03, 135.37, 135.84, 139.51 (Ar), 167.10 (C═O). IR: 1398, 1468, 1660, 2921, 3138 cm−1.

Workup

  1. distillationDistilled THF (25 mL)
  2. customresulting in the formation of a bright yellow precipitate
  3. extractionUpon completion the mixture was then extracted with EtOAc (15 mL)
  4. washwashed with saturated sodium bicarbonate (3×10 mL), water (3×10 mL)
  5. dry with materialdried (Na2SO4)
  6. customRecrystallisation of the cream/yellow residue from a minimum amount of boiling ethyl acetate and excess petrol

Sources & evidence

ORD record
ord-86eef68652c1472a9eb9f4897a9de72f
Source dataset
uspto-grants-2016_06
Patent number
US09358222B2

Reaction notes

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