Acetyl chloride → tert-butyl 2-(acetoxymethyl)-4-((tetrahydro-2H-pyran-2-yl)oxy)piperidine-1-carboxylate

Temperature

0 °C

To a solution of the product of step F (1.0 g, 3.7 mmol) in dichloromethane (20 mL) at 0° C. was added diisopropylethylamine (1.0 mL, 5.7 mmol) followed by acetyl chloride (0.32 mL, 4.4 mmol). The solution was stirred for 10 min at 0° C. followed by 45 min at ambient temperature. The reaction mixture was washed with NaHCO3 solution (3×15 mL) then NaCl solution (2×10 mL) and dried over Na2SO4. The mixture was filtered and the filtrate concentrated in vacuo to afford the crude product which was purified by flash column chromatography (SiO2, 19:1 to 4:1, hexanes/ethyl acetate) to give tert-butyl 2-(acetoxymethyl)-4-((tetrahydro-2H-pyran-2-yl)oxy)piperidine-1-carboxylate (701 mg, 68%) as a colorless oil: 1H NMR (CDCl3, 300 MHz) δ 4.69-4.51 (m, 3H), 4.22-3.83 (m, 5H), 3.53-3.48 (m, 3H), 3.23-3.18 (m, 1H), 2.05-2.03 (m, 3H), 1.84-1.55 (m, 7H), 1.41 (s, 9H).

1. waitfollowed by 45 min at ambient temperature
2. washThe reaction mixture was washed with NaHCO3 solution (3×15 mL)
3. dry with materialNaCl solution (2×10 mL) and dried over Na2SO4
4. filtrationThe mixture was filtered
5. concentrationthe filtrate concentrated in vacuo
6. customto afford the crude product which
7. customwas purified by flash column chromatography (SiO2, 19:1 to 4:1, hexanes/ethyl acetate)

ORD record

ord-e76fa58e60b1482383a99bc18fe41689

Source dataset

uspto-grants-2015_06

DOI

10.6084/m9.figshare.5104873.v1

Patent number

US09067949B2