Potassium Iodide → Alimix

HRID 345587Notes

Reaction equation

HRID 345587 reaction equation
Cl[CH2:2][CH2:3][CH2:4][O:5][C:6]1[CH:11]=[CH:10][C:9]([F:12])=[CH:8][CH:7]=1.[NH2:13][C:14]1[C:30]([Cl:31])=[CH:29][C:17]([C:18]([NH:20][C@H:21]2[CH2:26][CH2:25][NH:24][CH2:23][C@H:22]2[O:27][CH3:28])=[O:19])=[C:16]([O:32][CH3:33])[CH:15]=1.[I-].[K+]>C(N(CC)CC)C>[OH2:5].[NH2:13][C:14]1[C:30]([Cl:31])=[CH:29][C:17]([C:18]([NH:20][C@H:21]2[CH2:26][CH2:25][N:24]([CH2:2][CH2:3][CH2:4][O:5][C:6]3[CH:11]=[CH:10][C:9]([F:12])=[CH:8][CH:7]=3)[CH2:23][C@H:22]2[O:27][CH3:28])=[O:19])=[C:16]([O:32][CH3:33])[CH:15]=1

Participants

5

Reactant 3

HCID 4875Potassium IodideHCID 743911-(3-Chloropropoxy)-4-fluorobenzeneHCID 98616214-Amino-5-chloro-2-methoxy-N-[(3R,4S)-3-methoxypiperidin-4-YL]benzamide

Product 1

HCID 13677778AlimixYield 42.8%

Reagents, catalysts & solvents 1

HCID 8471TriethylamineSolvent

Conditions

Temperature
60 °C

Procedure

A mixture of 4.7 parts of 1-(3-chloropropoxy)-4-fluorobenzene, 3.015 parts of cis-4-amino-5-chloro-2-methoxy-N-(3-methoxy-4-piperidinyl)benzamide, 0.1 parts of potassium iodide, 3 parts of N,N-diethylethanamine and 45 parts of N,N-dimethylformiade was stirred and heated for 18 hours at 60° C. The reaction mixture was poured onto water. The precipitated product was filtered off and dissolved in trichloromethane. The solution was washed with water. The organic phase was separated, 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 oily residue was crystallized from 2-propanol. The product was filtered off and dried, yielding 3.11 parts (42.8%) of cis-4-amino-5-chloro-N-[1-[3-(4-fluorophenoxy)propyl]-3-methoxy-4-piperidinyl]-2-methoxybenzamide monohydrate; mp. 109.8° C. (compound 1).

Workup

  1. additionThe reaction mixture was poured onto water
  2. filtrationThe precipitated product was filtered off
  3. dissolutiondissolved in trichloromethane
  4. washThe solution was washed with water
  5. customThe organic phase was separated
  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 (90:10 by volume) as eluent
  11. customThe pure fractions were collected
  12. customthe eluent was evaporated
  13. customThe oily residue was crystallized from 2-propanol
  14. filtrationThe product was filtered off
  15. customdried

Sources & evidence

ORD record
ord-a36337ea83e14c01b1b64194d4dd7c8a
Source dataset
uspto-grants-1991_10
Patent number
US05057525

Reaction notes

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