Citric Acid → (S)-N-[2-(3,4-Dichlorophenyl)-4-[4-(2-oxopiperidino)-4-(pyrrolidin-1-ylcarbonyl) piperidino]butyl]-N-methylbenzamide citric acid salt

HRID 1489193Notes

Reaction equation

HRID 1489193 reaction equation
[Cl:1][C:2]1[CH:3]=[C:4]([C@H:9]([CH2:21][CH:22]=O)[CH2:10][N:11]([CH3:20])[C:12](=[O:19])[C:13]2[CH:18]=[CH:17][CH:16]=[CH:15][CH:14]=2)[CH:5]=[CH:6][C:7]=1[Cl:8].[O:24]=[C:25]1[CH2:30][CH2:29][CH2:28][CH2:27][N:26]1[C:31]1([C:37]([N:39]2[CH2:43][CH2:42][CH2:41][CH2:40]2)=[O:38])[CH2:36][CH2:35][NH:34][CH2:33][CH2:32]1.C([BH3-])#N.[Na+].[C:48]([OH:60])(=[O:59])[CH2:49][C:50]([CH2:55][C:56]([OH:58])=[O:57])([C:52]([OH:54])=[O:53])[OH:51]>CO.C(=O)(O)[O-].[Na+].C(O)(=O)C>[C:48]([OH:60])(=[O:59])[CH2:49][C:50]([CH2:55][C:56]([OH:58])=[O:57])([C:52]([OH:54])=[O:53])[OH:51].[Cl:1][C:2]1[CH:3]=[C:4]([C@H:9]([CH2:21][CH2:22][N:34]2[CH2:35][CH2:36][C:31]([N:26]3[CH2:27][CH2:28][CH2:29][CH2:30][C:25]3=[O:24])([C:37]([N:39]3[CH2:40][CH2:41][CH2:42][CH2:43]3)=[O:38])[CH2:32][CH2:33]2)[CH2:10][N:11]([CH3:20])[C:12](=[O:19])[C:13]2[CH:14]=[CH:15][CH:16]=[CH:17][CH:18]=2)[CH:5]=[CH:6][C:7]=1[Cl:8]

Participants

8

Reactant 4

HCID 311Citric AcidHCID 5003444Sodium cyanoborohydrideHCID 15381108(S)-N-[2-(3,4-Dichlorophenyl)-4-oxobutyl]-N-methylbenzamideHCID 229037314-(2-Oxopiperidino)-4-(pyrrolidin-1-ylcarbonyl)piperidine

Product 1

HCID 67732359(S)-N-[2-(3,4-Dichlorophenyl)-4-[4-(2-oxopiperidino)-4-(pyrrolidin-1-ylcarbonyl) piperidino]butyl]-N-methylbenzamide citric acid saltYield 100.6%

Reagents, catalysts & solvents 3

HCID 176Acetic AcidSolventHCID 887MethanolSolvent4×HCID 516892Sodium BicarbonateSolvent

Procedure

(S)-N-[2-(3,4-Dichlorophenyl)-4-oxobutyl]-N-methylbenzamide (350 mg) in methanol (3 mL) was added to a solution of 4-(2-oxopiperidino)-4-(pyrrolidin-1-ylcarbonyl)piperidine (330 mg) and acetic acid (0.07 mL) in methanol (5 mL). After 10 minutes, sodium cyanoborohydride (100 mg) in methanol (2 mL) was added in a single portion. After being stirred for 3 hours, the reaction mixture was diluted with aqueous sodium bicarbonate, stirred for 30 minutes, and extracted with dichloromethane. The organic extracts were dried, evaporated, and chromatographed, with dichloromethane:methanol (95:5) as eluent. The resulting material (410 mg) was dissolved in methanol containing 1 equivalent of citric acid (128 mg), evaporated, suspended and pulverized in ether, evaporated, and placed under high vacuum to give the title compound as a white solid (540 mg); MS: m/z=613(M+1), 542[(M+1)-pyrrolidine]. Analysis for C33H42Cl2N4 O3 ·1.40 H2O·0.65 (C2H5)2 O·1.0 C6H8O7 : Calculated: C, 56.83; H, 6.80; N, 6.37; Found: C, 56.89; H, 6.74; N, 6.27.

Workup

  1. stirringstirred for 30 minutes
  2. extractionextracted with dichloromethane
  3. customThe organic extracts were dried
  4. customevaporated
  5. customchromatographed, with dichloromethane:methanol (95:5) as eluent
  6. customevaporated
  7. customevaporated

Sources & evidence

ORD record
ord-2b6c23b483174a2abe48c12f28d492b2
Source dataset
uspto-grants-1997_10
Patent number
US05677317

Reaction notes

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