Beta-Propiolactone → tert-Butyl 1-(oxetan-3-yl)piperidin-4-yl carbamate

HRID 60241

Reaction equation

HRID 60241 reaction equation
[C:1]([O:5][C:6](=[O:14])[NH:7][CH:8]1[CH2:13][CH2:12][NH:11][CH2:10][CH2:9]1)([CH3:4])([CH3:3])[CH3:2].[O:15]1[CH2:18][CH2:17][C:16]1=O.C(O[BH-](OC(=O)C)OC(=O)C)(=O)C.[Na+]>ClCCCl>[C:1]([O:5][C:6](=[O:14])[NH:7][CH:8]1[CH2:13][CH2:12][N:11]([CH:17]2[CH2:18][O:15][CH2:16]2)[CH2:10][CH2:9]1)([CH3:4])([CH3:2])[CH3:3]

Participants

5

Reactant 3

HCID 2365Beta-PropiolactoneHCID 7238334-(N-Boc-amino)piperidineHCID 5049666Sodium triacetoxyborohydride

Product 1

HCID 56604528tert-Butyl 1-(oxetan-3-yl)piperidin-4-yl carbamateYield 67%

Reagents, catalysts & solvents 1

HCID 111,2-DichloroethaneSolvent2×

Procedure

To a suspension of piperidin-4-yl-carbamic acid tert-butyl ester (200 mg, 1.0 mmol) in DCE (6 mL) was added oxetanone (60 mg, 0.83 mmol) in DCE (2 mL). After 75 min, sodium triacetoxyborohydride (282 mg, 1.33 mmol) was added in one portion. After 20 hours at ambient temperature, the reaction mixture was loaded directly onto a 5 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, 5 g column, Si-SPE, 0-10% methanol in dichloromethane) afforded the title compound as a white solid (141 mg, 67%). 1H NMR (300 MHz, CDCl3): 4.62-4.61 (m, 4H), 4.44 (s, 1H), 3.46-3.45 (m, 2H), 2.67 (d, J=10.9 Hz, 2H), 2.02-1.88 (m, 4H), 1.44 (s, 9H).

Workup

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

Sources & evidence

ORD record
ord-21ed99da9d1943258608cfc03367be3a
Source dataset
uspto-grants-2016_09
Patent number
US09440976B2

Linked notes

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