Thionyl Chloride → 3-Chloro-3-(4-chlorophenyl)-2-(4-methylbenzyl)isoindolin-1-one

HRID 2199287Notes

Reaction equation

HRID 2199287 reaction equation
[Cl:1][C:2]1[CH:7]=[CH:6][C:5]([C:8]2(O)[C:16]3[C:11](=[CH:12][CH:13]=[CH:14][CH:15]=3)[C:10](=[O:17])[N:9]2[CH2:18][C:19]2[CH:24]=[CH:23][C:22]([CH3:25])=[CH:21][CH:20]=2)=[CH:4][CH:3]=1.S(Cl)([Cl:29])=O>CN(C=O)C>[Cl:29][C:8]1([C:5]2[CH:6]=[CH:7][C:2]([Cl:1])=[CH:3][CH:4]=2)[C:16]2[C:11](=[CH:12][CH:13]=[CH:14][CH:15]=2)[C:10](=[O:17])[N:9]1[CH2:18][C:19]1[CH:24]=[CH:23][C:22]([CH3:25])=[CH:21][CH:20]=1

Participants

4

Reactant 2

HCID 24386Thionyl ChlorideHCID 513497003-(4-Chlorophenyl)-3-hydroxy-2-(4-methylbenzyl)isoindolin-1-one

Product 1

HCID 513513953-Chloro-3-(4-chlorophenyl)-2-(4-methylbenzyl)isoindolin-1-one

Reagents, catalysts & solvents 1

HCID 6228DimethylformamideCatalyst

Procedure

Distilled THF (10 mL) was added to 3-(4-chlorophenyl)-3-hydroxy-2-(4-methylbenzyl)-isoindolin-1-one (400 mg, 1.13 mmol), thionyl chloride (295.8 mg, 2.48 mmol, 0.18 mL) and catalytic DMF (3 drops) as for general procedure B1. 3-Chloro-3-(4-chlorophenyl)-2-(4-methylbenzyl)isoindolin-1-one was produced as a viscous yellow oil (418 mg, 1.13 mmol) which was used immediately without further purification. Distilled THF (3 mL) was added to 3-chloro-3-(4-chlorophenyl)-2-(4-methylbenzyl)isoindolin-1-one (418.1 mg, 1.13 mmol) and the resultant solution added dropwise to cis-cyclopentene diol (285 mg, 2.85 mmol) and dried K2CO3 (390.41 mg, 2.85 mmol) in distilled THF (3 mL) as for general procedure B1. Removal of the solvent yielded the crude product as a green oil (359 g). Purification by flash column chromatography yielded the title product as a colourless viscous oil (242.1 mg, 0.55 mmol, 50%) 1H NMR: (300 MHz, DMSO) δ ppm 1.19 (m, 1H, H16/16′), 1.67, 2.05 (m, 1H, H16/16′) 2.21 (s, 3H, H12), 3.85 (m, 1H, HO, 4.06 (d, 1H, J=15.21 Hz, H9/9′), 4.32 (m, 1H, H15) 4.53 (d, 1H, J=15.21 Hz, H9/9′), 4.81, 5.74, (dd, 1H, H18/19) 5.20, 5.66 (dd, 1H, H18/19), 6.95 (m, 4H, H10, H11, H13, H14), 7.25 (m, 5H, H1-H5), 7.65 (m, 2H, H6-H7) 7.74 (d, 1H, H8). IR: 1380, 1467, 1699, 2922 cm−1. HR-MS (EI): Calculated mass: [M+H]+446.1517. Found: 446.1517.

Workup

  1. distillationDistilled THF (10 mL)

Sources & evidence

ORD record
ord-54aaaa0cf6d84542927144ef9351ae5e
Source dataset
uspto-grants-2016_06
Patent number
US09358222B2

Reaction notes

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