Cyclohexyl phenyl ketone → HCID 86680291, compound

HRID 2202606Notes

Reaction equation

HRID 2202606 reaction equation
[C:1]1([C:7]([CH:9]2[CH2:14][CH2:13][CH2:12][CH2:11][CH2:10]2)=[O:8])[CH:6]=[CH:5][CH:4]=[CH:3][CH:2]=1.[BH4-].[Na+].S(Cl)(Cl)=O.[C:21]([N:26]1[CH2:31][CH2:30][CH:29](O)[CH2:28][CH2:27]1)([O:23][CH2:24][CH3:25])=[O:22]>C(O)C.C(OCC)(=O)C.C1(C)C=CC=CC=1>[CH:1]1([CH:7]([C:9]2[CH:10]=[CH:11][CH:12]=[CH:13][CH:14]=2)[O:8][CH:29]2[CH2:30][CH2:31][N:26]([C:21]([O:23][CH2:24][CH3:25])=[O:22])[CH2:27][CH2:28]2)[CH2:6][CH2:5][CH2:4][CH2:3][CH2:2]1

Participants

8

Reactant 4

HCID 12837Cyclohexyl phenyl ketoneHCID 24386Thionyl Chloride2×HCID 96394Ethyl 4-hydroxypiperidine-1-carboxylateHCID 4311764Sodium borohydride

Product 1

HCID 86680291HCID 86680291, compoundYield 123%

Reagents, catalysts & solvents 3

HCID 702EthanolSolventHCID 1140TolueneSolventHCID 8857Ethyl AcetateSolvent

Procedure

Cyclohexyl phenyl ketone (5.0 g, 27 mmol) was dissolved in ethanol (50 mL) and cooled by ice. Sodium borohydride (510 mg, 13.5 mmol) was added thereto at 0° C. The completion of the addition, the mixture was heated to a room temperature, and the disappearance of the raw material was confirmed by TLC. The reaction solution was concentrated and then diluted with water, and the diluted solution was neutralized with a 1-N hydrochloric acid aqueous solution. Ethyl acetate was added thereto, the mixture was subjected to extraction. Then the extract was dried over sodium sulfate. The solvent was distilled off, and the residue was used for the next step without purification. The resulting viscous oil was dissolved in dichloromethane (10 mL), and thionyl chloride (10 mL, 140 mmol) was added dropwise thereto at a room temperature. After the dropping was completed, the completion of the reaction was confirmed by TLC. After the completion of the reaction, toluene was added to the reaction mixture, and unreacted thionyl chloride was distilled off. The resulting light-yellow oil and 1-carboethoxy-4-hydroxypiperidine (2.1 g, 12 mmol) were mixed, and the mixture was stirred at an oil bath temperature of 130° C. overnight. After the completion of the reaction was confirmed by TLC, the reaction mixture was allowed to cool down. Ethyl acetate was added to the resulting residue, and then the resulting mixture was washed with water. The organic layer was dried over sodium sulfate, and then the solvent was distilled off. Thus a brown oil was obtained. The resulting oil was purified by silica gel column chromatography (hexane/ethyl acetate (volume ratio)=10:1) to give the title compound (5.1 g, 510).

Workup

  1. temperaturecooled by ice
  2. customat 0° C
  3. additionThe completion of the addition
  4. concentrationThe reaction solution was concentrated
  5. additiondiluted with water
  6. additionEthyl acetate was added
  7. extractionthe mixture was subjected to extraction
  8. dry with materialThen the extract was dried over sodium sulfate
  9. distillationThe solvent was distilled off
  10. customthe residue was used for the next step without purification
  11. dissolutionThe resulting viscous oil was dissolved in dichloromethane (10 mL)
  12. customat a room temperature
  13. distillationwas distilled off
  14. temperatureto cool down
  15. washthe resulting mixture was washed with water
  16. dry with materialThe organic layer was dried over sodium sulfate
  17. distillationthe solvent was distilled off
  18. customThus a brown oil was obtained
  19. customThe resulting oil was purified by silica gel column chromatography (hexane/ethyl acetate (volume ratio)=10:1)

Sources & evidence

ORD record
ord-4128f0e5f7ff44edbe015c4236b9ab5b
Source dataset
uspto-grants-2016_06
Patent number
US09365553B2

Reaction notes

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