Isopropyl chloroformate → 1-methylethyl 4-[(1R)-1-hydroxyethyl]-1-piperidinecarboxylate

A solution of (1R)-1-(4-piperidinyl)ethanol acetic acid salt (1 g, 5.28 mmol) in water (10 mL) was cooled to 0° C. in an ice bath. A solution of K2CO3 (3.65 g, 26.4 mmol) in water (8 mL) was added, followed by dropwise addition of isopropyl chloroformate (1M in toluene, 21.1 mL, 21.1 mmol). The reaction mixture was stirred from 0° C. to ambient temperature over 2 h, then at ambient temperature overnight, diluted with CH2Cl2 (100 mL), washed with 1N HCl, water and brine, dried over Na2SO4, filtered, and the filtrate was concentrated to give a brown oil, which was dissolved in MeOH (15 mL). K2CO3 (1 g, 7.24 mmol) and water (5 mL) were added, and the mixture was stirred at ambient temperature overnight and extracted with CH2Cl2. The organic extracts were combined and washed with water, brine, dried over Na2SO4, filtered, and the filtrate was concentrated to give 1.11 g (98%) of 1-methylethyl 4-[(1R)-1-hydroxyethyl]-1-piperidinecarboxylate as a colorless oil, which was used without further purification (% ee not determined). 1H NMR (400 MHz, CDCl3): δ 4.88 (septet, 1H, J=6.2 Hz), 4.25-4.10 (m, 2H), 3.60-3.50 (m, 1H), 2.75-2.60 (m, 2H), 1.85-1.75 (m, 1H), 1.65-1.55 (m, 1H), 1.50-1.35 (m, 1H), 1.25-1.10 (m, 11H).

1. washwashed with 1N HCl, water and brine
2. dry with materialdried over Na2SO4
3. filtrationfiltered
4. concentrationthe filtrate was concentrated
5. customto give a brown oil, which
6. stirringthe mixture was stirred at ambient temperature overnight
7. extractionextracted with CH2Cl2
8. washwashed with water, brine
9. dry with materialdried over Na2SO4
10. filtrationfiltered
11. concentrationthe filtrate was concentrated

ORD record

ord-d40960657fa24e98a9af97d8140a1a57

Source dataset

uspto-grants-2012_01

DOI

10.6084/m9.figshare.5104873.v1

Patent number

US08101634B2