Triethylamine → tert-Butyl 4-formylpiperidine-1-carboxylate

Temperature

0 °C

To a cooled (0° C.) solution of 4-hydroxymethylpiperidine-1-carboxylic acid, 1,1-dimethylethyl ester (Example 36; 0.82 g, 3.8. mmol) and triethylamine (2.75 mL, 19.76 mmol) in dichloromethane (20 mL) was added sulfur trioxide pyridine complex (2.42 g, 15.2 mmol) in dimethylsulfoxide (10 mL) in three portions and the reaction was stirred at 0° C. for 3.5 h. Examination of the reaction by tlc indicated that some starting alcohol remained, so an additional quantity of sulfur trioxide pyridine complex (1.21 g, 7.6 mmol) in dimethylsulfoxide (5 mL) was added and the reaction was allowed to proceed for another 2 h at 0° C. The reaction mixture was partitioned between saturated sodium bicarbonate solution (60 mL) and diethyl ether/hexane (1:2, 125 mL) and the separated aqueous phase was re-extracted with diethyl ether/hexane (1:2, 2×50 mL). The combined organic extracts were washed with a 1M sodium dihydrogen phosphate solution (50 mL) and with brine (50 mL), then were dried (MgSO4), filtered and evaporated in vacuo. The resulting residual material was chromatographed over silica gel (25% ethyl acetate/petroleum ether) to give 4-formylpiperidine-1-carboxylic acid, 1,1-dimethylethyl ester (0.492 g, 61% yield) as a colorless oil.

1. customExamination of the reaction
2. waitto proceed for another 2 h at 0° C
3. customThe reaction mixture was partitioned between saturated sodium bicarbonate solution (60 mL) and diethyl ether/hexane (1:2, 125 mL)
4. extractionthe separated aqueous phase was re-extracted with diethyl ether/hexane (1:2, 2×50 mL)
5. washThe combined organic extracts were washed with a 1M sodium dihydrogen phosphate solution (50 mL) and with brine (50 mL)
6. dry with materialwere dried (MgSO4)
7. filtrationfiltered
8. customevaporated in vacuo
9. customThe resulting residual material was chromatographed over silica gel (25% ethyl acetate/petroleum ether)

ORD record

ord-21e15d7928ce4f748782d775d1635116

Source dataset

uspto-grants-2003_02

DOI

10.6084/m9.figshare.5104873.v1

Patent number

US06515124B2