Hydrochloric Acid → 4-Cyano-4-[3-cyclopentyloxy-4-(4-fluorobenzyloxy)phenyl)cyclohexan-1-one

HRID 2399429Notes

Reaction equation

HRID 2399429 reaction equation
[C:1]([C:3]1([C:10]2[CH:15]=[CH:14][C:13]([O:16][CH3:17])=[C:12]([O:18][CH:19]3[CH2:23][CH2:22][CH2:21][CH2:20]3)[CH:11]=2)[CH2:8][CH2:7][C:6](=[O:9])[CH2:5][CH2:4]1)#[N:2].Cl.C1(O)C=CC=CC=1.[F:32][C:33]1[CH:40]=[CH:39][C:36](CBr)=[CH:35][CH:34]=1.C(=O)([O-])[O-].[K+].[K+]>CO.O.CN(C)C=O>[C:1]([C:3]1([C:10]2[CH:15]=[CH:14][C:13]([O:16][CH2:17][C:36]3[CH:39]=[CH:40][C:33]([F:32])=[CH:34][CH:35]=3)=[C:12]([O:18][CH:19]3[CH2:23][CH2:22][CH2:21][CH2:20]3)[CH:11]=2)[CH2:8][CH2:7][C:6](=[O:9])[CH2:5][CH2:4]1)#[N:2]

Participants

9

Reactant 5

HCID 313Hydrochloric AcidHCID 996PhenolHCID 11430Potassium CarbonateHCID 680214-Fluorobenzyl bromideHCID 9861604SB-200473

Product 1

HCID 152952054-Cyano-4-[3-cyclopentyloxy-4-(4-fluorobenzyloxy)phenyl)cyclohexan-1-oneYield 78%

Reagents, catalysts & solvents 3

HCID 887MethanolSolventHCID 962WaterSolvent2×HCID 6228DimethylformamideSolvent

Conditions

Temperature
90 °C

Procedure

A solution of 4-cyano-4-[3-cyclopentyloxy-4-methoxyphenyl)cyclohexan-1-one (0.75 g, 2.4 mmol) and concentrated hydrochloric acid (2 mL) in methanol (10 mL) was heated at reflux under an argon atmosphere for 2 h. The mixture was cooled, was diluted with water and was extracted three times with methylene chloride. The organic extract was dried (magnesium sulfate) and was evaporated to the phenol (0.54 g, 92%). A vigorously stirred mixture of this phenol, 4-fluorobenzyl bromide (0.83 mL, 6.6 mmol) and potassium carbonate (0.92 g, 6.6 mmol) in dimethylformamide (12 mL) was heated under an argon atmosphere at 90° C. for 2 h. The mixture was allowed to cool, was diluted with water and was extracted three times with ether. The organic extract was dried (magnesium sulfate) and the solvent was removed in vacuo. Purification by flash chromatography, eluting with 30% ethyl acetate/hexanes, provided a white solid (0.6 g, 78%): m.p. 145°-146° C.

Workup

  1. temperatureat reflux under an argon atmosphere for 2 h
  2. temperatureThe mixture was cooled
  3. extractionwas extracted three times with methylene chloride
  4. extractionThe organic extract
  5. dry with materialwas dried (magnesium sulfate)
  6. customwas evaporated to the phenol (0.54 g, 92%)
  7. temperatureto cool
  8. extractionwas extracted three times with ether
  9. extractionThe organic extract
  10. dry with materialwas dried (magnesium sulfate)
  11. customthe solvent was removed in vacuo
  12. customPurification by flash chromatography
  13. washeluting with 30% ethyl acetate/hexanes

Sources & evidence

ORD record
ord-24ab631e934b4841a90e04ed668a7b84
Source dataset
uspto-grants-1995_09
Patent number
US05449686

Reaction notes

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