Dimethyl Sulfoxide → tert-Butyl 4-(2-oxoethyl)piperidine-1-carboxylate

Temperature

0 °C

Oxalyl chloride (2.2 mL, 25 mmol) was added to 75 mL of anhydrous CH2Cl2 at −78° C. DMSO (3.5 mL, 50 mmol) was then added dropwise over 5 min, and the resulting mixture was stirred for 15 min. 1-t-Butyloxycarbonyl-4-(2-hydroxyethyl)piperidine (2.29 g, 10 mmol, step A) was dissolved in 5 mL of anhydrous CH2Cl2 and added over 10 min to the above mixture. After stirring 30 min, DIEA (17.4 mL, 100 mmol) was added over 10 min. The mixture was then warmed to 0° C. and maintained at that temperature for 1 hr. After quenching with water, the reaction mixture was diluted with 75 mL of CH2Cl2 and the layers were separated. The organic phase was washed with 3×50 mL of water and dried over anhydrous magnesium sulfate. Solvent removal gave an oil, which was purified on silica gel using 20% EtOAc in hexane to give 2.05 g of the desired aldehyde which hardened overnight into an oily solid. NMR: 1.2 (m, 2H),1.5˜1.7 (m, 3H), 2.15 (d, 2H, J=3), 2.75 (m, 2H), 4.1 (m, 2H) 9.8(s, 1H).

1. additionadded over 10 min to the above mixture
2. stirringAfter stirring 30 min
3. temperaturemaintained at that temperature for 1 hr
4. customAfter quenching with water
5. additionthe reaction mixture was diluted with 75 mL of CH2Cl2
6. customthe layers were separated
7. washThe organic phase was washed with 3×50 mL of water
8. dry with materialdried over anhydrous magnesium sulfate
9. customSolvent removal
10. customgave an oil, which
11. customwas purified on silica gel using 20% EtOAc in hexane

ORD record

ord-d2fa7e57bcf34874b9f98c6d605df41b

Source dataset

uspto-grants-2001_06

DOI

10.6084/m9.figshare.5104873.v1

Patent number

US06248755B1