tert-Butyl acrylate → 3-{4-[4-(4-Chloro-3-trifluoromethyl-benzyloxy)-phenyl]-piperidin-1-yl}-propionic acid tert-butyl ester

HRID 2100677Notes

Reaction equation

C(OC([N:8]1[CH2:13][CH2:12][CH:11]([C:14]2[CH:19]=[CH:18][C:17]([O:20][CH2:21][C:22]3[CH:27]=[CH:26][C:25]([Cl:28])=[C:24]([C:29]([F:32])([F:31])[F:30])[CH:23]=3)=[CH:16][CH:15]=2)[CH2:10][CH2:9]1)=O)(C)(C)C.[C:33]([O:37][C:38]([CH3:41])([CH3:40])[CH3:39])(=[O:36])[CH:34]=[CH2:35]>C(O)(C(F)(F)F)=O.C(Cl)Cl>[C:38]([O:37][C:33](=[O:36])[CH2:34][CH2:35][N:8]1[CH2:9][CH2:10][CH:11]([C:14]2[CH:15]=[CH:16][C:17]([O:20][CH2:21][C:22]3[CH:27]=[CH:26][C:25]([Cl:28])=[C:24]([C:29]([F:31])([F:30])[F:32])[CH:23]=3)=[CH:18][CH:19]=2)[CH2:12][CH2:13]1)([CH3:41])([CH3:40])[CH3:39]

Participants

Conditions

Temperature: 90 °C

Procedure

4-[4-(4-Chloro-3-trifluoromethyl-benzyloxy)-phenyl]-piperidine-1-carboxylic acid tert-butyl ester (1 eq) is dissolved in 10% TFA/DCM and stirred for 30 minutes. After concentration, the residue is re-dissolved in DCM and washed with saturated NaHCO3 and brine. The organic layer is dried over Na2SO4 and concentrated. The residue is then dissolved in MeOH and t-butyl acrylate (2 eq) is added. The resulting solution is heated at 90° C. in microwave for 10 minutes. After concentration, purification by flash column chromatography (80% EtOAc/hexane) gave 3-{4-[4-(4-Chloro-3-trifluoromethyl-benzyloxy)-phenyl]-piperidin-1-yl}-propionic acid tert-butyl ester. [MS: (ES+) 498.2 (M+1)+].

Workup

concentrationAfter concentration
dissolutionthe residue is re-dissolved in DCM
washwashed with saturated NaHCO3 and brine
dry with materialThe organic layer is dried over Na2SO4
concentrationconcentrated
dissolutionThe residue is then dissolved in MeOH
concentrationAfter concentration, purification by flash column chromatography (80% EtOAc/hexane)

Sources & evidence

ORD record: ord-ea4827422dd7499eb8814aa11b10c838
Source dataset: uspto-grants-2009_08
DOI: 10.6084/m9.figshare.5104873.v1
Patent number: US07572811B2

Reaction notes

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