Phenol → HCID 67915707, compound

HRID 654188Notes

Reaction equation

HRID 654188 reaction equation
[N:1]1[CH:6]=[CH:5][C:4]([SH:7])=[CH:3][CH:2]=1.[H-].[Na+].C1([OH:16])C=CC=CC=1.F[B-](F)(F)F.[NH2:22][C:23]1[C:66]([Cl:67])=[CH:65][C:26]([C:27]([NH:29][C@H:30]2[CH2:35][CH2:34][N:33]([CH2:36][CH2:37][CH2:38][N+]3C(C4C=CC=CC=4)=CC(C4C=CC=CC=4)=CC=3C3C=CC=CC=3)[CH2:32][C@H:31]2[O:63][CH3:64])=[O:28])=[C:25]([O:68][CH3:69])[CH:24]=1>>[OH2:16].[NH2:22][C:23]1[C:66]([Cl:67])=[CH:65][C:26]([C:27]([NH:29][C@H:30]2[CH2:35][CH2:34][N:33]([CH2:36][CH2:37][CH2:38][S:7][C:4]3[CH:5]=[CH:6][N:1]=[CH:2][CH:3]=3)[CH2:32][C@H:31]2[O:63][CH3:64])=[O:28])=[C:25]([O:68][CH3:69])[CH:24]=1

Participants

5

Reactant 4

HCID 996Phenol2×HCID 24758Sodium hydrideHCID 86743796HCID 86743796, compoundHCID 178418431pyridine-4-thiol

Product 1

HCID 67915707HCID 67915707, compoundYield 19%

Procedure

A mixture of 2.8 parts of 4-pyridinethiol, 1.2 parts of a sodium hydride dispersion 50% and 45 parts of phenol was stirred for 4 hours at room temperature. Then there were added 7.5 parts of cis-1-[3-[4-[(4-amino-5-chloro-2-methoxybenzoyl)amino]-3-methoxy-1-piperidinyl]propyl]-2,4,6-triphenylpyridinium tetrafluoroborate and 30 parts of phenol. Stirring was continued for 4 hours at reflux. The reaction mixture was extracted five times with 100 parts of a hydrochloric acid solution 1N. The combined acid aqueous phases were treated with potassium hydroxide and extracted with dichloromethane. The extract was dried, filtered and evaporated. The residue was purified by column chromatography over silic gel using a mixture of trichloromethane and methanol, saturated with ammonia (95:5 by volume) as eluent. The pure fractions were collected and the eluent was evaporated. The residue was further purified by column chromatography (HPLC) over silica gel using a mixture of dichloromethane and methanol (95:5 by volume) as eluent. The pure fractions were collected and the eluent was evaporated. The residue was crystallized from acetonitrile. The product was filtered off and dried, yielding 0.88 parts (19%) of cis-4-amino-5-chloro-2-methoxy-N-[3-methoxy-1-[3-(4-pyridinylthio)propyl]-4-piperidinyl]benzamide monohydrate; mp. 114.3° C. (compound 59).

Workup

  1. stirringStirring
  2. waitwas continued for 4 hours
  3. temperatureat reflux
  4. extractionThe reaction mixture was extracted five times with 100 parts of a hydrochloric acid solution 1N
  5. additionThe combined acid aqueous phases were treated with potassium hydroxide
  6. extractionextracted with dichloromethane
  7. customThe extract was dried
  8. filtrationfiltered
  9. customevaporated
  10. customThe residue was purified by column chromatography over silic gel
  11. additiona mixture of trichloromethane and methanol
  12. customThe pure fractions were collected
  13. customthe eluent was evaporated
  14. customThe residue was further purified by column chromatography (HPLC) over silica gel using
  15. additiona mixture of dichloromethane and methanol (95:5 by volume) as eluent
  16. customThe pure fractions were collected
  17. customthe eluent was evaporated
  18. customThe residue was crystallized from acetonitrile
  19. filtrationThe product was filtered off
  20. customdried

Sources & evidence

ORD record
ord-32a582b181424870be88d6513fbeff76
Source dataset
uspto-grants-1992_07
Patent number
US05130312

Reaction notes

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