Ammonium Hydroxide → HCID 10408687, compound

HRID 1835287Notes

Reaction equation

HRID 1835287 reaction equation
[F:1][C:2]1[CH:15]=[CH:14][C:5]([C:6]([CH:8]2[CH2:13][CH2:12][NH:11][CH2:10][CH2:9]2)=[O:7])=[CH:4][CH:3]=1.[O:16]1[CH:18]([CH2:19][O:20][C:21]2[CH:26]=[CH:25][CH:24]=[CH:23][CH:22]=2)[CH2:17]1.[C:27](N1C=CN=C1)([N:29]1C=CN=C1)=[O:28].[OH-].[NH4+]>C(O)(C)C.C1COCC1.O>[F:1][C:2]1[CH:3]=[CH:4][C:5]([C:6]([CH:8]2[CH2:13][CH2:12][N:11]([CH2:17][CH:18]([O:16][C:27](=[O:28])[NH2:29])[CH2:19][O:20][C:21]3[CH:22]=[CH:23][CH:24]=[CH:25][CH:26]=3)[CH2:10][CH2:9]2)=[O:7])=[CH:14][CH:15]=1

Participants

8

Reactant 4

HCID 14923Ammonium HydroxideHCID 31217Phenyl glycidyl etherHCID 682631,1'-CarbonyldiimidazoleHCID 27244404-(4-Fluorobenzoyl)piperidine

Product 1

HCID 10408687HCID 10408687, compound

Reagents, catalysts & solvents 3

HCID 962WaterSolventHCID 3776IsopropanolSolventHCID 8028TetrahydrofuranSolvent

Procedure

A mixture of 4-(4-fluorobenzoyl)piperidine (5 mmol) and 1,2-epoxy-3-phenoxypropane (5 mmol) was refluxed in 30 ml of isopropanol for 4 h. This solution was then concentrated on a rotary evaporator and diluted with ethyl acetate. This mixture was then washed with brine, the resulting organic layer was dried and concentrated in vacuo to give a solid. This was recrystallized in a solution mixture of n-hexane and ethyl acetate to give a white solid. This was dissolved in THF (50 ml) and was added with 1,1′-carbonyl diimidazole (10 mmol) at 0° C. The reaction mixture was stirred at room temperature for 4 h, followed by the addition of excess ammonium hydroxide (10 ml) at 0° C. After 5 h stirring at room temperature, water was added to terminate the reaction. The organic layer was extracted 3 times with dichloromethane, dried and concentrated in vacuo. The residue was purified by column chromatography (ethyl acetate:hexane=1:2). The resulting carbamic acid 1-[4-(4-fluoro-benzoyl)-piperidin-1-ylmethyl]-2-phenoxy-ethyl ester was dissolved in THF and the solution was treated with a solution of HCl in ethyl ether. The resulting precipitate was filtered to give carbamic acid 1-[4-(4-fluoro-benzoyl)-piperidin-1-ylmethyl]-2-phenoxy-ethyl ester; hydrochloride.

Workup

  1. concentrationThis solution was then concentrated on a rotary evaporator
  2. additiondiluted with ethyl acetate
  3. washThis mixture was then washed with brine
  4. customthe resulting organic layer was dried
  5. concentrationconcentrated in vacuo
  6. customto give a solid
  7. customThis was recrystallized in a solution mixture of n-hexane and ethyl acetate
  8. customto give a white solid
  9. stirringAfter 5 h stirring at room temperature
  10. customto terminate
  11. customthe reaction
  12. extractionThe organic layer was extracted 3 times with dichloromethane
  13. customdried
  14. concentrationconcentrated in vacuo
  15. customThe residue was purified by column chromatography (ethyl acetate:hexane=1:2)
  16. dissolutionThe resulting carbamic acid 1-[4-(4-fluoro-benzoyl)-piperidin-1-ylmethyl]-2-phenoxy-ethyl ester was dissolved in THF
  17. additionthe solution was treated with a solution of HCl in ethyl ether
  18. filtrationThe resulting precipitate was filtered

Sources & evidence

ORD record
ord-d6fbc4e7d50d4d4abbbbc95336c132a7
Source dataset
uspto-grants-2004_08
Patent number
US06770659B2

Reaction notes

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