3,4-dihydro-2H-pyran → 1-tert-butyl 2-methyl 4-((tetrahydro-2H-pyran-2-yl)oxy)piperidine-1,2-dicarboxylate

To a stirred solution of the alcohol from step D (3.8 g, 15.0 mmol) in anhydrous dichloromethane (50 mL) was added dihydropyran (7.5 mL, 88.6 mmol) followed by p-toluenesulfonic acid monohydrate (71 mg, 0.4 mmol). After 3 h, triethylamine (0.42 mL, 3.0 mmol) was added and the reaction mixture was concentrated in vacuo. Ethyl acetate (100 mL) was added and the resulting solution was washed with brine (3×50 mL), dried over Na2SO4 and filtered. The filtrate was concentrated in vacuo and the residue purified by column chromatography (SiO2, 9:1 to 7:3, hexanes/ethyl acetate) to afford 1-tert-butyl 2-methyl 4-((tetrahydro-2H-pyran-2-yl)oxy)piperidine-1,2-dicarboxylate (5.0 g, 96%) as a colorless oil: 1H NMR (CDCl3, 400 MHz) δ 5.00-4.62 (m, 2H), 4.15-4.02 (m, 1H), 3.71 (t, J=7.2 Hz, 3H), 3.50-3.47 (m, 1H), 2.49 (br s, 1H), 1.95-1.70 (m, 4H), 1.60-1.42 (m, 13H), 1.27-1.24 (m, 4H).

1. concentrationthe reaction mixture was concentrated in vacuo
2. additionEthyl acetate (100 mL) was added
3. washthe resulting solution was washed with brine (3×50 mL)
4. dry with materialdried over Na2SO4
5. filtrationfiltered
6. concentrationThe filtrate was concentrated in vacuo
7. customthe residue purified by column chromatography (SiO2, 9:1 to 7:3, hexanes/ethyl acetate)

ORD 기록

ord-f74dc9802f474e469c4c5a6c7b325871

출처 데이터셋

uspto-grants-2015_06

DOI

10.6084/m9.figshare.5104873.v1

특허 번호

US09067949B2