Water → N-(2-fluoro-4-chloro-5-cyclopentyloxyphenyl)-3,4,5,6-tetrahydrophthalimide

HRID 1684329Notes

Reaction equation

HRID 1684329 reaction equation
[Cl:1][C:2]1[C:8]([O:9][CH:10]2[CH2:14][CH2:13][CH2:12][CH2:11]2)=[CH:7][C:5]([NH2:6])=[C:4]([F:15])[CH:3]=1.[C:16]1(=O)[O:21][C:19](=[O:20])[C:18]2[CH2:22][CH2:23][CH2:24][CH2:25][C:17]1=2.O>C(OCC)(=O)C>[Cl:1][C:2]1[C:8]([O:9][CH:10]2[CH2:14][CH2:13][CH2:12][CH2:11]2)=[CH:7][C:5]([N:6]2[C:19](=[O:20])[C:18]3[CH2:22][CH2:23][CH2:24][CH2:25][C:17]=3[C:16]2=[O:21])=[C:4]([F:15])[CH:3]=1

Participants

5

Reactant 3

HCID 962WaterHCID 124753,4,5,6-Tetrahydrophthalic anhydrideHCID 152793894-Chloro-5-(cyclopentyloxy)-2-fluorobenzenamine

Product 1

HCID 15279390N-(2-fluoro-4-chloro-5-cyclopentyloxyphenyl)-3,4,5,6-tetrahydrophthalimideYield 65%

Reagents, catalysts & solvents 1

HCID 8857Ethyl AcetateSolvent

Procedure

A solution of 4-chloro-5-cyclopentyloxy-2-fluoroaniline (0.50 g, 2.18 mmol) and 3,4,5,6-tetrahydrophthalic anhydride (0.398 g, 2.61 mmol) in acetic acids solution (3.0 mL) was stirred under reflux for 3 h. After completion of the reaction, water (20 mL) was added to the resulting reaction mixture and extraction was conducted with ethyl acetate (20 mL×3). The organic layers were dried with anhydrous magnesium sulfate and the solvent was distilled off under vacuum. The resulting pale yellow oil was separated and purified by silica gel column chromatography (ethyl acetate/hexane=1/8), giving N-(4-chloro-5-cyclopentyloxy-2-fluorophenyl)-3,4,5,6-tetrahydrophthalimide as a colorless clear oil (0.513 g, 1.41 mmol; yield=65%). This could be obtained as white solids upon addition of ethanol and subsequent recrystallization. MP: 69.0°-75.2° C. 1H-NMR(CDCl3,TMS,ppm): δ1.32-2.10(12H,m), 2.40(4H,m), 4.68(1H,m), 6.75(1H,d,JHF =7.0Hz), 7.20(1H, d,JHF =9.0Hz). IR (neat, cm-1): 1725, 1505, 1430, 1385, 1200.

Workup

  1. temperatureunder reflux for 3 h
  2. additionwas added to the resulting reaction mixture and extraction
  3. dry with materialThe organic layers were dried with anhydrous magnesium sulfate
  4. distillationthe solvent was distilled off under vacuum
  5. customThe resulting pale yellow oil was separated
  6. custompurified by silica gel column chromatography (ethyl acetate/hexane=1/8)

Sources & evidence

ORD record
ord-274ae2c87e51412db0f3ae67c11573a2
Source dataset
uspto-grants-1997_06
Patent number
US05639915

Reaction notes

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