Acetyl chloride → HCID 15096836, compound

HRID 846801Notes

Reaction equation

HRID 846801 reaction equation
[NH2:1][C:2]1[C:24]([Cl:25])=[CH:23][C:5]([C:6]([NH:8][C@H:9]2[CH2:14][CH2:13][N:12]([CH2:15][C:16]3[CH:21]=[CH:20][CH:19]=[CH:18][N:17]=3)[CH2:11][C@H:10]2[OH:22])=[O:7])=[C:4]([O:26][CH3:27])[CH:3]=1.[C:28](Cl)(=[O:30])[CH3:29].C(=O)([O-])[O-].[Na+].[Na+].[O:38]1CC[CH2:40][CH2:39]1>C(N(CC)CC)C>[C:28]([O:22][C@H:10]1[C@@H:9]([NH:8][C:6](=[O:7])[C:5]2[CH:23]=[C:24]([Cl:25])[C:2]([NH:1][C:39](=[O:38])[CH3:40])=[CH:3][C:4]=2[O:26][CH3:27])[CH2:14][CH2:13][N:12]([CH2:15][C:16]2[CH:21]=[CH:20][CH:19]=[CH:18][N:17]=2)[CH2:11]1)(=[O:30])[CH3:29]

Participants

6

Reactant 4

HCID 6367Acetyl chlorideHCID 8028Tetrahydrofuran2×HCID 10340Sodium CarbonateHCID 15096916HCID 15096916, compound

Product 1

HCID 15096836HCID 15096836, compound

Reagents, catalysts & solvents 1

HCID 8471TriethylamineSolvent

Procedure

To a stirred and cooled (ice-bath) solution of 6.64 parts of cis-4-amino-5-chloro-N-[3-hydroxy-1-(2-pyridinylmethyl)-4-piperidinyl]-2-methoxybenzamide in 68 parts of tetrahydrofuran were added 1.95 parts of N,N-diethylethanamine. Then there was added dropwise a solution of 1.41 parts of acetyl chloride in 27 parts of tetrahydrofuran at about 0° C. Upon completion, the mixture was allowed to reach slowly room temperature and stirring was continued for 18 hours at this temperature. Sodium carbonate was added and the whole was evaporated. The residue was taken up in water and the product was extracted with dichloromethane. The extract was washed with water, dried, filtered and evaporated. The residue was purified by column-chromatography over silica gel using a mixture of trichloromethane and methanol (95:5 by volume) as eluent. The pure fractions were collected and the eluent was evaporated. The residue was further purified by HPLC using a mixture of trichloromethane and methanol (97:3 by volume) as eluent. The first fraction was collected and the eluent was evaporated. The residue was suspended in petroleumether. The product was filtered off and dried, yielding 2.03 parts of cis-4-[[4-(acetylamino)-5-chloro-2-methoxybenzoyl]amino]-1-(2-pyridinylmethyl)-3-piperidinol acetate (ester); mp. 179.4° C. (compound 229).

Workup

  1. customto reach slowly room temperature
  2. stirringstirring
  3. customthe whole was evaporated
  4. extractionthe product was extracted with dichloromethane
  5. washThe extract was washed with water
  6. customdried
  7. filtrationfiltered
  8. customevaporated
  9. customThe residue was purified by column-chromatography over silica gel using
  10. additiona mixture of trichloromethane and methanol (95:5 by volume) as eluent
  11. customThe pure fractions were collected
  12. customthe eluent was evaporated
  13. customThe residue was further purified by HPLC
  14. additiona mixture of trichloromethane and methanol (97:3 by volume) as eluent
  15. customThe first fraction was collected
  16. customthe eluent was evaporated
  17. filtrationThe product was filtered off
  18. customdried

Sources & evidence

ORD record
ord-38a1346c92b944f8b0b511a7095c4c82
Source dataset
uspto-grants-1992_08
Patent number
US05137896

Reaction notes

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