3-Oxo-azetidine-1-carboxylic acid tert-butyl ester → 3-(2,2-Dimethylmorpholin-4-yl)azetidine-1-carboxylic acid tert-butyl ester

HRID 1945499Notes

Reaction equation

HRID 1945499 reaction equation
[CH3:1][C:2]1([CH3:8])[O:7][CH2:6][CH2:5][NH:4][CH2:3]1.[C:9]([O:13][C:14]([N:16]1[CH2:19][C:18](=O)[CH2:17]1)=[O:15])([CH3:12])([CH3:11])[CH3:10].C(O[BH-](OC(=O)C)OC(=O)C)(=O)C.[Na+]>ClCCCl.C(Cl)Cl>[C:9]([O:13][C:14]([N:16]1[CH2:19][CH:18]([N:4]2[CH2:5][CH2:6][O:7][C:2]([CH3:8])([CH3:1])[CH2:3]2)[CH2:17]1)=[O:15])([CH3:12])([CH3:10])[CH3:11]

Participants

6

Reactant 3

HCID 15194043-Oxo-azetidine-1-carboxylic acid tert-butyl esterHCID 5049666Sodium triacetoxyborohydrideHCID 189596742,2-Dimethylmorpholine

Product 1

HCID 596059313-(2,2-Dimethylmorpholin-4-yl)azetidine-1-carboxylic acid tert-butyl esterYield 81%

Reagents, catalysts & solvents 2

HCID 111,2-DichloroethaneSolventHCID 6344DichloromethaneSolvent

Procedure

A mixture of 2,2-dimethylmorpholine (260 mg, 2.26 mmol) and 3-oxoazetidine-1-carboxylic acid tert-butyl ester (464 mg, 2.71 mmol) in DCE (15 mL) was stirred at room temperature for 2 h before the addition of sodium triacetoxyborohydride (957 mg, 4.52 mmol). The resulting mixture was stirred for 16 h, then diluted with DCM and washed with H2O. The organic phase was dried (phase separator) and concentrated in vacuo. The resulting residue was purified by column chromatography (Si—PCC, EtOAc:cyclohexane, 0-40%) affording the title compound as an oil (492 mg, 81%). 1H NMR (CDCl3, 300 MHz): δ 3.95-3.85 (m, 2 H); 3.80-3.71 (m, 4 H); 3.07-2.88 (m, 1 H); 2.32-2.22 (m, 2 H); 2.14-2.06 (m, 2 H); 1.44 (s, 9 H); 1.25 (s, 6 H).

Workup

  1. washwashed with H2O
  2. customThe organic phase was dried (phase separator)
  3. concentrationconcentrated in vacuo
  4. customThe resulting residue was purified by column chromatography (Si—PCC, EtOAc:cyclohexane, 0-40%)

Sources & evidence

ORD record
ord-fcfc02af73c14c37a3e8c6dd0433ec2c
Source dataset
uspto-grants-2013_03
Patent number
US08394796B2

Reaction notes

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