Water → HCID 18758364, compound

HRID 433320Notes

Reaction equation

HRID 433320 reaction equation
Cl.[NH2:2][CH:3]([C:8]1[CH:13]=[CH:12][C:11]([O:14][CH3:15])=[C:10]([O:16][CH:17]2[CH2:21][CH2:20][CH2:19][CH2:18]2)[CH:9]=1)[CH2:4][CH:5]([OH:7])[CH3:6].[C:22]([NH:25][C:26]1[CH:36]=[CH:35][CH:34]=[C:28]2[C:29]([O:31][C:32](=O)[C:27]=12)=[O:30])(=[O:24])[CH3:23].C(N(CC)CC)C.O>CN(C=O)C>[CH:17]1([O:16][C:10]2[CH:9]=[C:8]([CH:3]([N:2]3[C:32](=[O:31])[C:27]4[C:28](=[CH:34][CH:35]=[CH:36][C:26]=4[NH:25][C:22](=[O:24])[CH3:23])[C:29]3=[O:30])[CH2:4][CH:5]([OH:7])[CH3:6])[CH:13]=[CH:12][C:11]=2[O:14][CH3:15])[CH2:21][CH2:20][CH2:19][CH2:18]1

Participants

6

Reactant 4

HCID 962WaterHCID 8471TriethylamineHCID 2261213-Acetamidophthalic AnhydrideHCID 67431395HCID 67431395, compound

Product 1

HCID 18758364HCID 18758364, compound

Reagents, catalysts & solvents 1

HCID 6228DimethylformamideSolvent

Conditions

Temperature
85 °C

Procedure

A stirred mixture of 4-amino-4-(3-cyclopentyloxy-4-methoxyphenyl)butan-2-ol hydrochloride(1.20 g, 3.80 mmol), 3-acetamidophthalic anhydride (0.78 g, 3.80 mmol) and triethylamine (0.38 g, 3.80 mmol) in DMF (15 mL) was heated at 80-90° C. for 7 hours. The mixture was allowed to cool to room temperature and poured into water (80 mL). The resulting mixture was extracted with EtOAC (3×30 mL). The combined ethyl acetate extracts were washed with water (30 mL), brine (30 mL) and dried over magnesium sulfate. The solvent was removed in vacuo and the residue was purified by chromatography (Silica gel, methylene chloride: EtOAC 8:2) to give N-{2-1-(3-cyclopentyloxy-4-meth-oxyphenyl)-3-hydroxybutyl]-1,3-dioxoisoindolin-4-yl}acetamide (1.3 g, 73%) as a white solid: 1H NMR (CDCl3) δ9.53 (s, 1H), 8.71 (d, J=8.4 Hz, 1H), 7.63 (t, J=7.7 Hz, 1H), 7.48 (d, J=7.3 Hz, 1H), 7.08-7.03 (m, 2H), 6.82 (d, J=8.2 Hz, 1H), 5.57-5.51 (dd, J=4.2, 11.6 Hz, 1H), 4.78 (m, 1H), 3.81 (s, 3H), 3.77-3.74 (m, 1H), 2.91-2.81 (m, 1H), 2.25 (s, 3H), 2.13-1.60 (m, 10H), 1.29 (d, J=6.1 Hz, 3H); 13C NMR (CDCl3) δ170.38, 169.21, 168.06, 149.70, 147.50, 137.33, 135.84, 131.54, 131.20, 124.71, 120.28, 117.93, 115.31, 115.07, 111.55, 80.45, 64.89, 55.97, 51.35, 39.92, 32.73, 24.91, 24.04, 23.76, 21.02.

Workup

  1. temperatureto cool to room temperature
  2. extractionThe resulting mixture was extracted with EtOAC (3×30 mL)
  3. washThe combined ethyl acetate extracts were washed with water (30 mL), brine (30 mL)
  4. dry with materialdried over magnesium sulfate
  5. customThe solvent was removed in vacuo
  6. customthe residue was purified by chromatography (Silica gel, methylene chloride: EtOAC 8:2)
  7. customto give N-{2-1-(3-cyclopentyloxy-4-meth-oxyphenyl)-3-hydroxybutyl]-1,3-dioxoisoindolin-4-yl}acetamide (1.3 g, 73%) as a white solid

Sources & evidence

ORD record
ord-7a5505813a5c42ec9a6eeb802c2c4062
Source dataset
uspto-grants-2003_12
Patent number
US06667316B1

Reaction notes

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