Tetrahydrofuran → HCID 15096950, compound

HRID 345602Notes

Reaction equation

HRID 345602 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.[O:32]1CC[CH2:34][CH2:33]1>C(N(CC)CC)C>[C:33]([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]([NH2:1])=[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:32])[CH3:34]

Participants

4

Reactant 2

HCID 8028TetrahydrofuranHCID 13677777HCID 13677777, compound

Product 1

HCID 15096950HCID 15096950, compound

Reagents, catalysts & solvents 1

HCID 8471TriethylamineSolvent

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 2.02 parts of N,N-diethylethanamine. After cooling to 0° C., there was dried dropwise a solution of 1.4 parts of acetyl chloride in 9 parts of tetrahydrofurane at a temperature below 0° C. Upon completion, stirring was continued for a while while cooling in an ice-bath. The reaction mixture was allowed to reach slowly room temperature and stirring was continued overnight at room temperature. The reaction mixture was evaporated and the residue was taken up in a sodium carbonate solution in water. The product was extracted with methylbenzene. 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 separated by HPLC using a mixture of trichloromethane, hexane and methanol (48:48:4 by volume) as eluent. The second fraction (B-isomer) was collected and the eluent was evaporated. The residue was suspended in petroleumether. The product was filtered off and dried, yielding 1.7 parts of cis-4-[(4-amino-5-chloro-2-methoxybenzoyl)amino]-1-[3-(4-fluorophenoxy)propyl]-3-piperidinol acetate (ester); mp. 58.8° C. (compound 232).

Workup

  1. dry with materialthere was dried dropwise a solution of 1.4 parts of acetyl chloride in 9 parts of tetrahydrofurane at a temperature below 0° C
  2. temperaturewhile cooling in an ice-bath
  3. customto reach slowly room temperature
  4. stirringstirring
  5. customThe reaction mixture 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 by column-chromatography over silica gel using
  12. additiona mixture of trichloromethane and methanol (95:5 by volume) as eluent
  13. customThe pure fractions were collected
  14. customthe eluent was evaporated
  15. customThe residue was further separated by HPLC
  16. additiona mixture of trichloromethane, hexane and methanol (48:48:4 by volume) as eluent
  17. customThe second fraction (B-isomer) was collected
  18. customthe eluent was evaporated
  19. filtrationThe product was filtered off
  20. customdried

Sources & evidence

ORD record
ord-9feb5cfea6b34c088a02dc743c4a83c4
Source dataset
uspto-grants-1991_10
Patent number
US05057525

Reaction notes

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