Triethylamine → cis-3-chloro-5-ethyl-6-hydroxy-2-methoxy-N-[3-methoxy-1-[4-oxo-4-(1-pyrrolidinyl)butyl]-4-piperidinyl]benzamide

HRID 1110395Notes

Reaction equation

HRID 1110395 reaction equation
[NH2:1][C@H:2]1[CH2:7][CH2:6][N:5]([CH2:8][CH2:9][CH2:10][C:11]([N:13]2[CH2:17][CH2:16][CH2:15][CH2:14]2)=[O:12])[CH2:4][C@H:3]1[O:18][CH3:19].[Cl:20][C:21]1[C:22]([O:33][CH3:34])=[C:23]([C:27]([OH:32])=[C:28]([CH2:30][CH3:31])[CH:29]=1)[C:24](Cl)=[O:25].C(N(CC)CC)C>ClC(Cl)Cl>[Cl:20][C:21]1[C:22]([O:33][CH3:34])=[C:23]([C:27]([OH:32])=[C:28]([CH2:30][CH3:31])[CH:29]=1)[C:24]([NH:1][C@H:2]1[CH2:7][CH2:6][N:5]([CH2:8][CH2:9][CH2:10][C:11](=[O:12])[N:13]2[CH2:14][CH2:15][CH2:16][CH2:17]2)[CH2:4][C@H:3]1[O:18][CH3:19])=[O:25]

Participants

5

Reactant 3

HCID 8471TriethylamineHCID 134328933-Chloro-5-ethyl-6-hydroxy-2-methoxybenzoyl chlorideHCID 70047197cis-1-[4-(4-Amino-3-methoxy-1-piperidinyl)-1-oxobutyl]pyrrolidine

Product 1

HCID 86744371cis-3-chloro-5-ethyl-6-hydroxy-2-methoxy-N-[3-methoxy-1-[4-oxo-4-(1-pyrrolidinyl)butyl]-4-piperidinyl]benzamideYield 71.9%

Reagents, catalysts & solvents 1

HCID 6212ChloroformSolvent2×

Procedure

To a stirred solution of 4.04 parts of cis-1-[4-(4-amino-3-methoxy-1-piperidinyl)-1-oxobutyl]pyrrolidine in 225 parts of trichloromethane was added a solution of 4.15 parts of 3-chloro-5-ethyl-6-hydroxy-2-methoxybenzoyl chloride in trichloromethane. After stirring for 15 minutes at room temperature, 1.9 parts of N,N-diethylethanamine were added and the whole was stirred overnight at room temperature. The reaction mixture was washed with water, saturated with ammonia and twice with water, dried, filtered and evaporated. The residue was purified by column chromatography over silica gel using a mixture of trichloromethane and methanol, saturated with ammonia (90:10 by volume) as eluent. The pure fractions were collected and the eluent was evaporated. The residue was crystallized from 2,2'-oxybispropane. The product was filtered off and dried, yielding 5.2 parts (71.9%) of cis-3-chloro-5-ethyl-6-hydroxy-2-methoxy-N-[3-methoxy-1-[4-oxo-4-(1-pyrrolidinyl)butyl]-4-piperidinyl]benzamide; mp. 90.8° C. (compound 67).

Workup

  1. stirringthe whole was stirred overnight at room temperature
  2. washThe reaction mixture was washed with water, saturated with ammonia and twice with water
  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
  8. customThe pure fractions were collected
  9. customthe eluent was evaporated
  10. customThe residue was crystallized from 2,2'-oxybispropane
  11. filtrationThe product was filtered off
  12. customdried

Sources & evidence

ORD record
ord-52e2208b986e4dca954695e43386284e
Source dataset
uspto-grants-1990_12
Patent number
US04975439

Reaction notes

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