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

HRID 2179409Notes

Reaction equation

HRID 2179409 reaction equation
[OH:1][CH:2]1[CH2:7][CH2:6][N:5]([C:8]([O:10][C:11]([CH3:14])([CH3:13])[CH3:12])=[O:9])[CH:4]([C:15]([O:17][CH3:18])=[O:16])[CH2:3]1.[O:19]1[CH:24]=[CH:23][CH2:22][CH2:21][CH2:20]1.C(N(CC)CC)C>ClCCl.O.C1(C)C=CC(S(O)(=O)=O)=CC=1>[O:19]1[CH2:24][CH2:23][CH2:22][CH2:21][CH:20]1[O:1][CH:2]1[CH2:7][CH2:6][N:5]([C:8]([O:10][C:11]([CH3:12])([CH3:13])[CH3:14])=[O:9])[CH:4]([C:15]([O:17][CH3:18])=[O:16])[CH2:3]1

Participants

6

Reactant 3

HCID 80803,4-dihydro-2H-pyranHCID 8471TriethylamineHCID 10400342HCID 10400342, compound

Product 1

HCID 681099661-tert-butyl 2-methyl 4-((tetrahydro-2H-pyran-2-yl)oxy)piperidine-1,2-dicarboxylateYield 97.1%

Reagents, catalysts & solvents 2

HCID 521998p-Toluenesulfonic acid monohydrateCatalystHCID 6344DichloromethaneSolvent

Procedure

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).

Workup

  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)

Sources & evidence

ORD record
ord-f74dc9802f474e469c4c5a6c7b325871
Source dataset
uspto-grants-2015_06
Patent number
US09067949B2

Reaction notes

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