Beta-Propiolactone → 1-(Oxetan-3-yl)piperidin-4-ol

HRID 60243

Reaction equation

HRID 60243 reaction equation
[NH:1]1[CH2:6][CH2:5][CH:4]([OH:7])[CH2:3][CH2:2]1.[O:8]1[CH2:11][CH2:10][C:9]1=O.C(O[BH-](OC(=O)C)OC(=O)C)(=O)C.[Na+]>ClCCCl>[O:8]1[CH2:11][CH:10]([N:1]2[CH2:6][CH2:5][CH:4]([OH:7])[CH2:3][CH2:2]2)[CH2:9]1

Participants

5

Reactant 3

HCID 2365Beta-PropiolactoneHCID 79341Piperidin-4-olHCID 5049666Sodium triacetoxyborohydride

Product 1

HCID 552828561-(Oxetan-3-yl)piperidin-4-olYield 60.4%

Reagents, catalysts & solvents 1

HCID 111,2-DichloroethaneSolvent

Procedure

To a suspension of piperidin-4-ol (364 mg, 3.6 mmol) in DCE (30 mL) was added oxetanone (216 mg, 3.0 mmol). After 2 hours, sodium triacetoxyborohydride (1.02 g, 4.8 mmol) was added in one portion. After 20 hours at ambient temperature, the reaction mixture was loaded directly onto a 20 g SCX-2 cartridge which was washed with methanol, then 2N ammonia in methanol. Concentration of the combined basic fractions in-vacuo followed by flash chromatography of the resultant residue (silica, 10 g column, Si-SPE, 0-10% methanol in dichloromethane) afforded the title compound as a colourless oil (285 mg, 52%). 1H NMR (300 MHz, CDCl3): 4.64-4.63 (m, 4H), 3.77-3.77 (m, 1H), 3.49-3.47 (m, 1H), 2.65-2.55 (m, 2H), 2.04 (t, J=10.5 Hz, 2H), 1.94-1.93 (m, 2H), 1.62-1.61 (m, 2H), 1.47 (d, J=4.5 Hz, 1H).

Workup

  1. waitAfter 20 hours at ambient temperature
  2. washwas washed with methanol

Sources & evidence

ORD record
ord-d6349a6d3c57474ebe8699734d2a7464
Source dataset
uspto-grants-2016_09
Patent number
US09440976B2

Linked notes

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