Ammonia → HCID 67914513, compound

HRID 846807Notes

Reaction equation

HRID 846807 reaction equation
[NH2:1][C:2]1[C:34]([Cl:35])=[CH:33][C:5]([C:6]([NH:8][C@H:9]2[CH2:14][CH2:13][N:12]([CH2:15][CH2:16][CH:17]([OH:30])[C:18]([C:23]3[CH:28]=[CH:27][C:26]([F:29])=[CH:25][CH:24]=3)(OC)[O:19]C)[CH2:11][C@H:10]2[O:31][CH3:32])=[O:7])=[C:4]([O:36][CH3:37])[CH:3]=1.Cl.N>O>[NH2:1][C:2]1[C:34]([Cl:35])=[CH:33][C:5]([C:6]([NH:8][C@H:9]2[CH2:14][CH2:13][N:12]([CH2:15][CH2:16][CH:17]([OH:30])[C:18]([C:23]3[CH:28]=[CH:27][C:26]([F:29])=[CH:25][CH:24]=3)=[O:19])[CH2:11][C@H:10]2[O:31][CH3:32])=[O:7])=[C:4]([O:36][CH3:37])[CH:3]=1

Participants

5

Reactant 3

HCID 222AmmoniaHCID 313Hydrochloric AcidHCID 15096927HCID 15096927, compound

Product 1

HCID 67914513HCID 67914513, compoundYield 16%

Reagents, catalysts & solvents 1

HCID 962WaterSolvent2×

Procedure

A mixture of 2.88 parts of cis-4-amino-5-chloro-N-[1-[4-(4-fluorophenyl)-3-hydroxy-4,4-dimethoxybutyl]-3-methoxy-4-piperidinyl]-2-methoxybenzamide, 30 parts of concentrate hydrochloric acid and 25 parts of water was stirred for 18 hours at room temperature. 100 Parts of water were added and the whole was alkalized with ammonia. The precipitated product was filtered off and taken up in trichloromethane. 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 (95:5 by volume) saturated with ammonia, as eluent. The pure fractions were collected and the eluent was evaporated. The residue was taken up in benzene. Upon the addition of petroleumether, the product was precipitated. It was filtered off and dried, yielding 0.47 parts (16%) of cis-4-amino-5-chloro-N-[1-[4-(4-fluorophenyl)-3-hydroxy-4-oxobutyl]-3-methoxy-4-piperidinyl]-2-methoxybenzamide; mp. 146.4° C. (compound 238).

Workup

  1. filtrationThe precipitated product was filtered off
  2. customThe organic phase was separated
  3. customdried
  4. filtrationfiltered
  5. customevaporated
  6. customThe residue was purified by column-chromatography over silica gel using
  7. additiona mixture of trichloromethane and methanol (95:5 by volume) saturated with ammonia
  8. customThe pure fractions were collected
  9. customthe eluent was evaporated
  10. additionUpon the addition of petroleumether
  11. customthe product was precipitated
  12. filtrationIt was filtered off
  13. customdried

Sources & evidence

ORD record
ord-3e6dba5fe5f24906b8a3550786c8be8e
Source dataset
uspto-grants-1992_08
Patent number
US05137896

Reaction notes

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