Methyl Isobutyl Ketone → N-[4-(methoxymethyl)-1-(1-methyl-2-phenylethyl)-4-piperidinyl]-N-phenylpropanamide ethanedioate

HRID 1973824Notes

Reaction equation

HRID 1973824 reaction equation
[CH3:1][CH:2]([OH:10])[CH2:3][C:4]1[CH:9]=[CH:8][CH:7]=[CH:6][CH:5]=1.[CH3:11][O:12][CH2:13][C:14]1([N:20]([C:25]2[CH:30]=[CH:29][CH:28]=[CH:27][CH:26]=2)[C:21](=[O:24])[CH2:22][CH3:23])[CH2:19][CH2:18][NH:17][CH2:16][CH2:15]1.[C:31](=[O:34])([O-:33])[O-].[Na+].[Na+].CC(C)CC(=O)C>O>[C:2]([OH:10])(=[O:12])[C:31]([OH:33])=[O:34].[CH3:11][O:12][CH2:13][C:14]1([N:20]([C:25]2[CH:26]=[CH:27][CH:28]=[CH:29][CH:30]=2)[C:21](=[O:24])[CH2:22][CH3:23])[CH2:19][CH2:18][N:17]([CH:2]([CH3:1])[CH2:3][C:4]2[CH:9]=[CH:8][CH:7]=[CH:6][CH:5]=2)[CH2:16][CH2:15]1

Participants

6

Reactant 4

HCID 7909Methyl Isobutyl KetoneHCID 10340Sodium CarbonateHCID 941851-Phenyl-2-propanolHCID 162172Noralfentanil

Product 1

HCID 12298099N-[4-(methoxymethyl)-1-(1-methyl-2-phenylethyl)-4-piperidinyl]-N-phenylpropanamide ethanedioate

Reagents, catalysts & solvents 1

HCID 962WaterSolvent2×

Procedure

A mixture of 3.54 parts of α-methylphenethyl alcohol, methanesulfonate ester, 4.1 parts of N-[4-(methoxymethyl)-4-piperidinyl]-N-phenylpropanamide, 3.97 parts of sodium carbonate and 160 parts of 4-methyl-2-pentanone is stirred and refluxed for 24 hours with water-separator. After cooling, water is added and the product is extracted with trichloromethane. The extract is washed with water, dried, filtered and evaporated. The residue is purified by column-chromatography over silica gel using a mixture of benzene and 10% of methanol as eluent. The pure fractions are collected and the eluent is evaporated. The residue is converted into the ethanediolate salt in 2-propanol. The salt is filtered off, washed with 2-propanol and dried, yielding N-[4-(methoxymethyl)-1-(1-methyl-2-phenylethyl)-4-piperidinyl]-N-phenylpropanamide ethanedioate; mp. 196.8° C.

Workup

  1. temperatureAfter cooling
  2. extractionthe product is extracted with trichloromethane
  3. washThe extract is washed with water
  4. customdried
  5. filtrationfiltered
  6. customevaporated
  7. customThe residue is purified by column-chromatography over silica gel using
  8. additiona mixture of benzene and 10% of methanol as eluent
  9. customThe pure fractions are collected
  10. customthe eluent is evaporated
  11. filtrationThe salt is filtered off
  12. washwashed with 2-propanol
  13. customdried

Sources & evidence

ORD record
ord-21027ee945a64597bb583b2d2c9ebbd6
Source dataset
uspto-grants-1976_12
Patent number
US03998834

Reaction notes

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