Acetic Acid → 1-{2-[4-(3,5-Dimethoxybenzyl)piperazin-1-yl]ethyl}-3,3-bis(4-fluorophenyl)pyrrolidin-2-one

HRID 1667132Notes

Reaction equation

[F:1][C:2]1[CH:7]=[CH:6][C:5]([C:8]2([C:22]3[CH:27]=[CH:26][C:25]([F:28])=[CH:24][CH:23]=3)[CH2:12][CH2:11][N:10]([CH2:13][CH2:14][N:15]3[CH2:20][CH2:19][NH:18][CH2:17][CH2:16]3)[C:9]2=[O:21])=[CH:4][CH:3]=1.[CH3:29][O:30][C:31]1[CH:32]=[C:33]([CH:36]=[C:37]([O:39][CH3:40])[CH:38]=1)[CH:34]=O.C(O)(=O)C>CO.ClCCl>[CH3:40][O:39][C:37]1[CH:36]=[C:33]([CH:32]=[C:31]([O:30][CH3:29])[CH:38]=1)[CH2:34][N:18]1[CH2:19][CH2:20][N:15]([CH2:14][CH2:13][N:10]2[CH2:11][CH2:12][C:8]([C:5]3[CH:6]=[CH:7][C:2]([F:1])=[CH:3][CH:4]=3)([C:22]3[CH:23]=[CH:24][C:25]([F:28])=[CH:26][CH:27]=3)[C:9]2=[O:21])[CH2:16][CH2:17]1

Participants

Conditions

Temperature: 40 °C

Procedure

To a solution of the product from Example 63C (1.85 g, 4.80 mmol) in methanol/dichloromethane (50 mL) was added 3,5-dimethoxybenzaldehyde (0.80 g, 4.80 mmol), macroporous-cyanoborohydride resin (8.09 g, 4.80 mmol, 2.24 mol/g) and acetic acid (1.6 mL, 4.80 mmol). The reaction was stirred at 40° C. for 18 hours under an atmosphere of nitrogen. The reaction was cooled to room temperature, filtered and concentrated. Silica gel chromatography eluting with 3% methanol/dichloromethane gave the title compound. The title compound was dissolved in methanol (10 mL) and treated with HCl (1.25 M in methanol, 5.1 mL), concentrated and dried under vacuum to give the title compound as the corresponding hydrochloride salt. MS (DCI) m/z 536.3 (M+H)+.

Workup

temperatureThe reaction was cooled to room temperature
filtrationfiltered
concentrationconcentrated
washSilica gel chromatography eluting with 3% methanol/dichloromethane

Sources & evidence

ORD record: ord-fb898bdcaa154af0a2f03beaf4a86e35
Source dataset: uspto-grants-2011_10
DOI: 10.6084/m9.figshare.5104873.v1
Patent number: US08044069B2

Reaction notes

Loading…