Acetyl chloride → HCID 15096837, compound

HRID 846802Notes

Reaction equation

HRID 846802 reaction equation
[NH2:1][C:2]1[C:28]([Cl:29])=[CH:27][C:5]([C:6]([NH:8][C@H:9]2[CH2:14][CH2:13][N:12]([CH2:15][CH2:16][CH2:17][O:18][C:19]3[CH:24]=[CH:23][C:22]([F:25])=[CH:21][CH:20]=3)[CH2:11][C@H:10]2[OH:26])=[O:7])=[C:4]([O:30][CH3:31])[CH:3]=1.C(N(CC)CC)C.[C:39](Cl)(=[O:41])[CH3:40].[O:43]1CC[CH2:45][CH2:44]1>>[C:39]([O:26][C@H:10]1[C@@H:9]([NH:8][C:6](=[O:7])[C:5]2[CH:27]=[C:28]([Cl:29])[C:2]([NH:1][C:44](=[O:43])[CH3:45])=[CH:3][C:4]=2[O:30][CH3:31])[CH2:14][CH2:13][N:12]([CH2:15][CH2:16][CH2:17][O:18][C:19]2[CH:20]=[CH:21][C:22]([F:25])=[CH:23][CH:24]=2)[CH2:11]1)(=[O:41])[CH3:40]

Participants

5

Reactant 4

HCID 6367Acetyl chlorideHCID 8028Tetrahydrofuran2×HCID 8471TriethylamineHCID 13677777HCID 13677777, compound

Product 1

HCID 15096837HCID 15096837, compound

Conditions

Temperature
0 °C

Procedure

To a stirred solution of 7.5 parts of cis-4-amino-5-chloro-N-[1-[3-(4-fluorophenoxy)propyl]-3-hydroxy-4-piperidinyl]-2-methoxybenzamide in 68 parts of tetrahydrofuran were added dropwise 1.94 parts of N,N-diethylethanamine. After cooling to 0° C., 1.4 parts of acetyl chloride dissolved in 9 parts of tetrahydrofuran were added dropwise at a temperature below 0° C. Upon completion, stirring was continued for a while in an ice-bath. The mixture was allowed to reach slowly room temperature and stirring was continued overnight at room temperature. The solvent was evaporated and the residue was taken up in a saturate sodium carbonate solution. The product was extracted with methylbenzene. The extract was washed with water, dried, filtered and evaporated. The residue was purified twice by column-chromatography over silica gel using first a mixture of trichloromethane and methanol (95:5 by volume) and then a mixture of trichloromethane, hexane and methanol (48:48:4 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 0.59 parts of cis-4-[[4-(acetylamino)-5-chloro-2-methoxybenzoyl]amino]-1-[3-(4-fluorophenoxy)-propyl]-3-piperidinol acetate (ester); mp. 172.2° C. (compound 231).

Workup

  1. additionwere added dropwise at a temperature below 0° C
  2. customwas continued for a while in an ice-bath
  3. customto reach slowly room temperature
  4. stirringstirring
  5. customThe solvent was evaporated
  6. extractionThe product was extracted with methylbenzene
  7. washThe extract was washed with water
  8. customdried
  9. filtrationfiltered
  10. customevaporated
  11. customThe residue was purified twice by column-chromatography over silica gel using first
  12. additiona mixture of trichloromethane and methanol (95:5 by volume)
  13. additiona mixture of trichloromethane, hexane and methanol (48:48:4 by volume) as eluent
  14. customThe first fraction was collected
  15. customthe eluent was evaporated
  16. filtrationThe product was filtered off
  17. customdried

Sources & evidence

ORD record
ord-47f97c04702e4047bece03a941d367bc
Source dataset
uspto-grants-1992_08
Patent number
US05137896

Reaction notes

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