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

HRID 1082194Notes

Reaction equation

HRID 1082194 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]

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-b95a5a4dc6e84a01a57b796cebd7e2a6
Source dataset
uspto-grants-1996_12
Patent number
US05589489

Reaction notes

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