Sodium borohydride → N-[1-(2-hydroxy-1-methyl-2-phenylethyl)-4-(methoxymethyl)-4-piperidinyl]-N-phenylpropanamide

HRID 1448324Notes

Reaction equation

HRID 1448324 reaction equation
[C:1]([CH:9]([N:11]1[CH2:16][CH2:15][C:14]([N:20]([C:25]2[CH:30]=[CH:29][CH:28]=[CH:27][CH:26]=2)[C:21](=[O:24])[CH2:22][CH3:23])([CH2:17][O:18][CH3:19])[CH2:13][CH2:12]1)[CH3:10])(=[O:8])[C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][CH:3]=1.[BH4-].[Na+]>CO>[OH:8][CH:1]([C:2]1[CH:3]=[CH:4][CH:5]=[CH:6][CH:7]=1)[CH:9]([N:11]1[CH2:16][CH2:15][C:14]([N:20]([C:25]2[CH:26]=[CH:27][CH:28]=[CH:29][CH:30]=2)[C:21](=[O:24])[CH2:22][CH3:23])([CH2:17][O:18][CH3:19])[CH2:13][CH2:12]1)[CH3:10]

Participants

4

Reactant 2

HCID 4311764Sodium borohydrideHCID 12298105N-[1-(1-benzoylethyl)-4-(methoxymethyl)-4-piperidinyl]-N-phenylpropanamide

Product 1

HCID 12298106N-[1-(2-hydroxy-1-methyl-2-phenylethyl)-4-(methoxymethyl)-4-piperidinyl]-N-phenylpropanamide

Reagents, catalysts & solvents 1

HCID 887MethanolSolvent

Procedure

To a stirred solution of 13.2 parts of N-[1-(1-benzoylethyl)-4-(methoxymethyl)-4-piperidinyl]-N-phenylpropanamide in 164 parts of methanol are added portionwise 1.34 parts of sodium borohydride (slightly exothermic reaction). Upon completion, stirring is continued first for 2 hours at 35° C. and further overnight at room temperature. The reaction mixture is evaporated. The residue is taken up in 50 parts of water and the whole is warmed for a while. After cooling, the product is extracted three times with 75 parts of trichloromethane. The combined extracts are washed with water, dried, filtered and evaporated. The oily residue is purified twice by column-chromatography over silicagel using a mixture of trichloromethane and 3% of methanol as eluent. The pure fractions are collected and the eluent is evaporated. The oily residue is triturated in petroleumether. The product is filtered off, crystallized from 2,2'-oxybispropane and a drop of 4-methyl-2-pentanone, filtered off again and dried at 110° C., yielding N-[1-(2-hydroxy-1-methyl-2-phenylethyl)-4-(methoxymethyl)-4-piperidinyl]-N-phenylpropanamide; mp. 154.2° C.

Workup

  1. customslightly exothermic reaction)
  2. customThe reaction mixture is evaporated
  3. temperaturethe whole is warmed for a while
  4. temperatureAfter cooling
  5. extractionthe product is extracted three times with 75 parts of trichloromethane
  6. washThe combined extracts are washed with water
  7. customdried
  8. filtrationfiltered
  9. customevaporated
  10. customThe oily residue is purified twice by column-chromatography over silicagel
  11. additiona mixture of trichloromethane and 3% of methanol as eluent
  12. customThe pure fractions are collected
  13. customthe eluent is evaporated
  14. customThe oily residue is triturated in petroleumether
  15. filtrationThe product is filtered off
  16. customcrystallized from 2,2'-oxybispropane
  17. filtrationa drop of 4-methyl-2-pentanone, filtered off again
  18. customdried at 110° C.

Sources & evidence

ORD record
ord-c5022f93a98e45d7b33f70626ac14ea5
Source dataset
uspto-grants-1979_12
Patent number
US04179569

Reaction notes

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