Potassium Hydroxide → 5-[(3r)-3-(4-Trifluoromethyl-phenoxy)pyrrolidin-1-yl]-5-methyl-2,2-diphenylhexanamide

HRID 450937Notes

Reaction equation

[OH-:1].[K+].[F:3][C:4]([F:38])([F:37])[C:5]1[CH:36]=[CH:35][C:8]([O:9][C@@H:10]2[CH2:14][CH2:13][N:12]([C:15]([CH3:34])([CH3:33])[CH2:16][CH2:17][C:18]([C:27]3[CH:32]=[CH:31][CH:30]=[CH:29][CH:28]=3)([C:21]3[CH:26]=[CH:25][CH:24]=[CH:23][CH:22]=3)[C:19]#[N:20])[CH2:11]2)=[CH:7][CH:6]=1>CC(O)(CC)CC>[F:38][C:4]([F:37])([F:3])[C:5]1[CH:6]=[CH:7][C:8]([O:9][C@@H:10]2[CH2:14][CH2:13][N:12]([C:15]([CH3:34])([CH3:33])[CH2:16][CH2:17][C:18]([C:21]3[CH:26]=[CH:25][CH:24]=[CH:23][CH:22]=3)([C:27]3[CH:28]=[CH:29][CH:30]=[CH:31][CH:32]=3)[C:19]([NH2:20])=[O:1])[CH2:11]2)=[CH:35][CH:36]=1

Participants

Conditions

Temperature: 25 °C

Procedure

Potassium hydroxide (23 mg, 0.406 mmol) was added to a solution of example 25 (10 mg, 0.0203 mmol) in 3-methyl-3-pentanol (2 mL) and the mixture was heated under reflux for 16 hours. The solution was cooled to 25° C. and potassium hydroxide (23 mg, 0.406 mmol) was added and the solution was heated under reflux for an additional 24 hours. The reaction mixture was then cooled to room temperature, concentrated in vacuo and the residue was purified by column chromatography on silica gel, eluting with ethyl acetate:methanol:0.88 ammonia, 95:5:0.5. to afford the title compound as a colourless gum in 68% yield, 7 mg.

Workup

temperaturethe mixture was heated
temperatureunder reflux for 16 hours
temperaturethe solution was heated
temperatureunder reflux for an additional 24 hours
temperatureThe reaction mixture was then cooled to room temperature
concentrationconcentrated in vacuo
customthe residue was purified by column chromatography on silica gel
washeluting with ethyl acetate

Sources & evidence

ORD record: ord-88bd451a393f4d808227353e7589f45d
Source dataset: uspto-grants-2013_07
DOI: 10.6084/m9.figshare.5104873.v1
Patent number: US08486992B2

Reaction notes

Loading…