tert-Butyl 4-(methoxy(methyl)carbamoyl)piperidine-1-carboxylate → tert-Butyl 4-formylpiperidine-1-carboxylate

Temperature

0 °C

4-(methoxy-methyl-carbamoyl)-piperidine-1-carboxylic acid tert-butyl ester (1.0 eq, 16.4 mmol) was dissolved in 100 ml dry tetrahydrofurane under inert atmosphere. This solution was added dropwise over a period of 1 h to a suspension of lithiumalanate (3.0 eq, 49.6 mmol) in 70 ml dry tetrahydrofurane at −50° C. During the adding of the mixture, the temperature was held at −50° C. and then allowed to warm to 0° C. within 3 h. The mixture was cooled to −78° C. and quenched carefully with 100 ml 1 M citric acid. The mixture was warmed up to r.t. and diluted with 400 ml ethylacetate. The phases were separated and the aqueous phase was extracted 3 times with 70 ml ethylacetate. The combined organic layers were extracted 3 times with 100 ml 1 M citric acid, aqueous sodium carbonate and 2 times with 100 ml brine, dried over MgSO4 and filtrated. The solvent was removed and the residue was purified by distillation resulting in a yield of 85%

1. additionDuring the adding of the mixture
2. customwas held at −50° C.
3. temperatureThe mixture was cooled to −78° C.
4. customquenched carefully with 100 ml 1 M citric acid
5. temperatureThe mixture was warmed up to r.t.
6. additiondiluted with 400 ml ethylacetate
7. customThe phases were separated
8. extractionthe aqueous phase was extracted 3 times with 70 ml ethylacetate
9. extractionThe combined organic layers were extracted 3 times with 100 ml 1 M citric acid, aqueous sodium carbonate and 2 times with 100 ml brine
10. dry with materialdried over MgSO4
11. filtrationfiltrated
12. customThe solvent was removed
13. distillationthe residue was purified by distillation
14. customresulting in a yield of 85%

ORD record

ord-ddb70f0e7a0844bfb6d91e7519af496c

Source dataset

uspto-grants-2012_01

DOI

10.6084/m9.figshare.5104873.v1

Patent number

US08106048B2