Trifluoroacetic acid → 2,2-Dimethylpropionic acid piperidin-4-ylmethyl ester

HRID 1191493Notes

Reaction equation

HRID 1191493 reaction equation
C(OC([N:8]1[CH2:13][CH2:12][CH:11]([CH2:14][O:15][C:16](=[O:21])[C:17]([CH3:20])([CH3:19])[CH3:18])[CH2:10][CH2:9]1)=O)(C)(C)C.C(O)(C(F)(F)F)=O>C(Cl)Cl>[NH:8]1[CH2:13][CH2:12][CH:11]([CH2:14][O:15][C:16](=[O:21])[C:17]([CH3:19])([CH3:18])[CH3:20])[CH2:10][CH2:9]1

Participants

4

Reactant 2

HCID 6422Trifluoroacetic acidHCID 689141014-(2,2-Dimethylpropionyloxymethyl)piperidine-1-carboxylic acid t-butyl ester

Product 1

HCID 689120142,2-Dimethylpropionic acid piperidin-4-ylmethyl esterYield 33%

Reagents, catalysts & solvents 1

HCID 6344DichloromethaneSolvent

Procedure

To 4-hydroxymethyl-piperidine-1-carboxylic acid tert-butylester (480 mg, 2.1 mmol) dissolved in dry DMF (10 ml) was added NaH (120 mg, 3.0 mmol, 55-65% in mineral oil) and the mixture was warmed to 60° C. for 2 h. The mixture was allowed to cool to rt and then pivaloyl chloride (0.1.6 ml, 1.3 mmol) was added. The reaction was allowed to stir over night and then poured into water and the mixture was extracted with ether. The combined organic phases were washed with brine, dried (Na2SO4), filtered, concentrated under reduced pressure and the oily residue was purified by Flash column chromatography (SiO2; heptane/EtOAc 70:30) to yield 4-(2,2-dimethylpropionyloxymethyl)piperidine-1-carboxylic acid t-butyl ester as an oil. Deprotection of 4-(2,2-dimethylpropionyloxymethyl)piperidine-1-carboxylic acid t-butyl ester was conducted using the method (CH2Cl2:TFA; 1:1) to yield the title compound as an oil (85 mg, 0.43 mmol, 33%). This crude was used without further purification.

Sources & evidence

ORD record
ord-c8b4c205cddb48b0a035674860e968eb
Source dataset
uspto-grants-2014_03
Patent number
US08680115B2

Reaction notes

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