Dimethylformamide → trans-3-Hydroxy-4-[(phenylmethyl)amino]-1-piperidineacetonitrile

HRID 1165039Notes

Reaction equation

HRID 1165039 reaction equation
[C:1]1([CH2:7][NH:8][C@@H:9]2[CH2:14][CH2:13][NH:12][CH2:11][C@H:10]2[OH:15])[CH:6]=[CH:5][CH:4]=[CH:3][CH:2]=1.CN(C)C=O.Cl[CH2:22][C:23]#[N:24]>C(N(CC)CC)C>[OH:15][C@H:10]1[C@H:9]([NH:8][CH2:7][C:1]2[CH:2]=[CH:3][CH:4]=[CH:5][CH:6]=2)[CH2:14][CH2:13][N:12]([CH2:22][C:23]#[N:24])[CH2:11]1

Participants

5

Reactant 3

HCID 6228DimethylformamideHCID 7856ChloroacetonitrileHCID 13677852rac-(3R,4R)-4-(benzylamino)piperidin-3-ol

Product 1

HCID 14854945trans-3-Hydroxy-4-[(phenylmethyl)amino]-1-piperidineacetonitrileYield 76.2%

Reagents, catalysts & solvents 1

HCID 8471TriethylamineSolvent

Procedure

To a stirred and heated (±70° C.) solution of 14.44 parts of trans-4-[(phenylmethyl)amino]-3-piperidinol in 189 parts of N,N-dimethylformamide were added 5.81 parts of chloroacetonitrile. After the addition of 9.7 parts of N,N-diethylethanamine, stirring was continued overnight at 70° C. After evaporation, the residue was taken up in dichloromethane. The organic layer was washed with a sodium carbonate solution in water, dried, filtered and evaporated. The residue was purified by column chromatography over silica gel using a mixture of trichloromethane and methanol (90:10 by volume) as eluent. The pure fractions were collected and the eluent was evaporated. The residue was suspended in 2,2'-oxybispropane. The product was filtered off and dried, yielding 13.1 parts (76.2%) of trans-3-hydroxy-4-[(phenylmethyl)amino]-1-piperidineacetonitrile; mp. 113.2° C. (interm. 16).

Workup

  1. stirringstirring
  2. customAfter evaporation
  3. washThe organic layer was washed with a sodium carbonate solution in water
  4. customdried
  5. filtrationfiltered
  6. customevaporated
  7. customThe residue was purified by column chromatography over silica gel using
  8. additiona mixture of trichloromethane and methanol (90:10 by volume) as eluent
  9. customThe pure fractions were collected
  10. customthe eluent was evaporated
  11. filtrationThe product was filtered off
  12. customdried

Sources & evidence

ORD record
ord-e3a35d84e19d48d0aaa91be04ea9d766
Source dataset
uspto-grants-1990_03
Patent number
US04906643

Reaction notes

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