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Acetic Acid → 3-[1-(3,4-Dichlorophenyl)-3-(4-hydroxy-4-phenylpiperidino)propyl]-2-methyl-2,3-dihydroiso-indol-1-one

HRID 1738932
Notes
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Reaction equation

HRID 1738932 reaction equation
[Cl:1][C:2]1[CH:3]=[C:4]([CH:9]([CH:13]2[C:21]3[C:16](=[CH:17][CH:18]=[CH:19][CH:20]=3)[C:15](=[O:22])[N:14]2[CH3:23])[CH2:10][CH:11]=O)[CH:5]=[CH:6][C:7]=1[Cl:8].[OH:24][C:25]1([C:31]2[CH:36]=[CH:35][CH:34]=[CH:33][CH:32]=2)[CH2:30][CH2:29][NH:28][CH2:27][CH2:26]1.C(O)(=O)C.C([BH3-])#N.[Na+]>CO.C(=O)(O)[O-].[Na+]>[Cl:1][C:2]1[CH:3]=[C:4]([CH:9]([CH:13]2[C:21]3[C:16](=[CH:17][CH:18]=[CH:19][CH:20]=3)[C:15](=[O:22])[N:14]2[CH3:23])[CH2:10][CH2:11][N:28]2[CH2:29][CH2:30][C:25]([OH:24])([C:31]3[CH:36]=[CH:35][CH:34]=[CH:33][CH:32]=3)[CH2:26][CH2:27]2)[CH:5]=[CH:6][C:7]=1[Cl:8]
ParticipantsProcedureWorkupSources & evidenceReaction notes

Participants

7

Reactant 4

HCID 176Acetic AcidHCID 963874-Phenylpiperidin-4-olHCID 5003444Sodium cyanoborohydrideHCID 218397793-(3,4-dichlorophenyl)-3-(2-methyl-3-oxo-2,3-dihydro-1H-isoindol-1-yl)propionaldehyde

Product 1

HCID 218397863-[1-(3,4-Dichlorophenyl)-3-(4-hydroxy-4-phenylpiperidino)propyl]-2-methyl-2,3-dihydroiso-indol-1-oneYield 63.5%

Reagents, catalysts & solvents 2

HCID 887MethanolSolventHCID 516892Sodium BicarbonateSolvent

Procedure

A solution of 3-(3,4-dichlorophenyl)-3-(2-methyl-3-oxo-2,3-dihydro-1H-isoindol-1-yl)propionaldehyde (0.112 g) in methanol (5 mL) was treated with 4-hydroxy-4-phenylpiperidine (0.057 g) and the pH was adjusted to 6 by adding acetic acid. After treating with sodium cyanoborohydride (0.030 g), the reaction mixture was stirred at ambient temperature for 16 hours, diluted with a saturated solution of sodium bicarbonate, and extracted with dichloromethane. The organic layers were dried and evaporated to obtain 3-[1-(3,4-dichlorophenyl)-3-(4-hydroxy-4-phenylpiperidino)propyl]-2-methyl-2,3-dihydroiso-indol-1-one as a foam (0.104 g). This material was transformed into the hydrochloride salt as follows. The above product was dissolved in dry dichloromethane (2 mL) and treated with HCl in ether (2 mL). The resulting solution was diluted with anhydrous ether, stirred for 2 hours and the resulting precipitate was collected to afford the title compound (0.075 g); mp 160° C. (dec); MS: m/z=509(M+1); NMR: 1.79 (broad,2), 3.32 (s,3), 3.75 (broad,1), 4.88 (m,1), 5.44 (s,1), 6.80-7.95 (m,12). Analysis for C29H30Cl2N2O2.HCl.0.5 H2O: Calculated: C, 62.76; H, 5.81; N, 5.13; Found: C, 62.79; H, 5.89; N, 4.89.

Workup

  1. extractionextracted with dichloromethane
  2. customThe organic layers were dried
  3. customevaporated

Sources & evidence

ORD record
ord-882cfe91b3d94e90abe321448f422bd2
Source dataset
uspto-grants-1999_10
DOI
10.6084/m9.figshare.5104873.v1
Patent number
US05965576

Reaction notes

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On this pageParticipantsProcedureWorkupSources & evidenceReaction notes