Cesium carbonate → 2-{5-[1-(1-Ethyl-propyl)-piperidin-3-yl]-4'-trifluoromethyl-biphenyl-3-yl}-4-methyl-pentanoic acid ethyl ester

HRID 889710Notes

Reaction equation

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

Participants

Conditions

Temperature: 78 °C

Procedure

To a solution of compound 33b, 4-Methyl-2-(5-piperidin-3-yl-4′-trifluoromethyl-biphenyl-3-yl)-pentanoic acid ethyl ester (42 mg, 0.093 mmol) in CH3CN (0.5 ml) was added 1-iodo-3-Bromopentane (21.0 mg, 0. 14 mmol) and cesium carbonate (61.0 mg, 0.186 mmol). The reaction was heated to 78° C. overnight. The subsequent addition of the reactants as described above and allowing the reaction to continue over a second night, resulted in ˜75% product: starting material. The reaction was cooled to room temperature, concentrated in vacuo, diluted with EtOAc, washed with NaHCO3, and brine. The solution was filtered, and concentrated, then purified via silica gel chromatography to give the product as a clear oil. (32.7 mg, 68% ) Calculated for C31H42F3NO2 (M+H) 517.67, Found 518.4.

Workup

additionThe subsequent addition of the reactants
customthe reaction
waitto continue over a second night

Sources & evidence

ORD record: ord-bc1a46842fbd44fba38a6d65b6cdb7f6
Source dataset: uspto-grants-2012_08
DOI: 10.6084/m9.figshare.5104873.v1
Patent number: US08252935B2

Reaction notes

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