Water → 4-(2,2-Dimethylpropionyloxymethyl)piperidine-1-carboxylic acid t-butyl ester

HRID 1986825Notes

Reaction equation

[C:1]([O:5][C:6]([N:8]1[CH2:13][CH2:12][CH:11]([CH2:14][OH:15])[CH2:10][CH2:9]1)=[O:7])([CH3:4])([CH3:3])[CH3:2].[H-].[Na+].[C:18](Cl)(=[O:23])[C:19]([CH3:22])([CH3:21])[CH3:20].O>CN(C=O)C>[C:1]([O:5][C:6]([N:8]1[CH2:13][CH2:12][CH:11]([CH2:14][O:15][C:18](=[O:23])[C:19]([CH3:22])([CH3:21])[CH3:20])[CH2:10][CH2:9]1)=[O:7])([CH3:4])([CH3:3])[CH3:2]

Participants

Conditions

Temperature: 60 °C

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.

Workup

temperatureto cool to rt
extractionthe mixture was extracted with ether
washThe combined organic phases were washed with brine
dry with materialdried (Na2SO4)
filtrationfiltered
concentrationconcentrated under reduced pressure
customthe oily residue was purified by Flash column chromatography (SiO2; heptane/EtOAc 70:30)

Sources & evidence

ORD record: ord-91b7a53cfcac4d03b71dda0388e27fff
Source dataset: uspto-grants-2009_06
DOI: 10.6084/m9.figshare.5104873.v1
Patent number: US07550459B2

Reaction notes

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