Propylamine → 3-(4-Chlorophenyl)-3-hydroxy-2-propylisoindolin-1-one

HRID 1916972Notes

Reaction equation

HRID 1916972 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.[CH2:26]([NH2:29])[CH2:27][CH3:28]>C(OCC)(=O)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:29]2[CH2:26][CH2:27][CH3:28])=[CH:13][CH:14]=1

Participants

5

Reactant 3

HCID 7852PropylamineHCID 8471TriethylamineHCID 126920383-Chloro-3-(4-chlorophenyl)-2-benzofuran-1(3H)-one

Product 1

HCID 513495613-(4-Chlorophenyl)-3-hydroxy-2-propylisoindolin-1-oneYield 78.6%

Reagents, catalysts & solvents 1

HCID 8857Ethyl AcetateSolvent

Procedure

Distilled THF (20 mL) was added to 3-chloro-3-(4-chlorophenyl)-3H-isobenzofuran-1-one (535.4 mg, 1.91 mmol) followed by triethylamine (398.9 mg, 0.549 mL, 3.94 mmol) and n-propylamine (159.8 mg, 0.22 mL, 1.792 mmol). 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). Recrysallisation from a minimum amount of boiling ethyl acetate and an excess of petrol yielded the title product as a white crystalline solid (425 mg, 1.409 mmol, 77%). 1H NMR: (300 Hz, CDCl3) δ ppm 0.76 (t, 3H, H11), 1.45 (m, 2H, H10), 2.86 (m, 1H, H9), 3.36 (m, 1H, H9′), 7.16 (d, 1H, H5), 7.38 (dd, 4H, H1-H4), 7.45 (m, 2H, H6-H7), 7.70 (d, 1H, H8). 13C NMR: (75 Hz, DMSO); δ 11.87 (N—CH2—CH2—CH3), 21.96 (N—CH2—CH2), 40.69 (N—CH2), 90.50 (O—C—N), 122.75, 122.99, 128.24, 128.76, 129.58, 131.04, 131.24, 132.73, 133.13, 139.94, 149.59 (Ar), 166.96 (C═O). Mp: 201.5-201.7° C. IR: 1466, 1608, 1664, 2968, 3157 cm−1.

Workup

  1. distillationDistilled THF (20 mL)
  2. extractionUpon completion the mixture was then extracted with EtOAc (15 mL)
  3. washwashed with saturated sodium bicarbonate (3×10 mL), water (3×10 mL)
  4. dry with materialdried (Na2SO4)

Sources & evidence

ORD record
ord-43c3b0add7dc4d52b5d12a39161a5f95
Source dataset
uspto-grants-2013_12
Patent number
US08618158B2

Reaction notes

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