Acetic Acid → HCID 90460454, compound

HRID 588832Notes

Reaction equation

HRID 588832 reaction equation
[Cl:1][C:2]1[C:17]([Cl:18])=[CH:16][C:5]([CH2:6][NH:7][C:8]([CH:10]2[CH2:15][CH2:14][NH:13][CH2:12][CH2:11]2)=[O:9])=[C:4]([O:19][CH3:20])[CH:3]=1.O=[C:22]1[CH2:25][N:24]([C:26]([O:28][C:29]([CH3:32])([CH3:31])[CH3:30])=[O:27])[CH2:23]1.CC(O)=O>CO>[Cl:1][C:2]1[C:17]([Cl:18])=[CH:16][C:5]([CH2:6][NH:7][C:8]([CH:10]2[CH2:11][CH2:12][N:13]([CH:22]3[CH2:23][N:24]([C:26]([O:28][C:29]([CH3:32])([CH3:31])[CH3:30])=[O:27])[CH2:25]3)[CH2:14][CH2:15]2)=[O:9])=[C:4]([O:19][CH3:20])[CH:3]=1

Participants

5

Reactant 3

HCID 176Acetic AcidHCID 15194043-Oxo-azetidine-1-carboxylic acid tert-butyl esterHCID 90462975HCID 90462975, compound

Product 1

HCID 90460454HCID 90460454, compoundYield 19.6%

Reagents, catalysts & solvents 1

HCID 887MethanolSolvent

Procedure

A mixture of N-(4,5-dichloro-2-methoxybenzyl)piperidine-4-carboxamide (750 mg, 2.37 mmol), tert-butyl 3-oxoazetidine-1-carboxylate (607 mg, 3.55 mmol), AcOH (1 mL) and MeOH (5 mL) was stirred at reflux for 2 h. To this mixture, NaBH3(CN) (0.74 g, 11.85 mmol) was added and the resulting mixture was stirred at 60° C. for 16 h. The mixture was allowed to cool to room temperature and partitioned between NH4Cl aqueous solution and ethyl acetate. The organic layer was washed with water and brine, dried over Na2SO4 and concentrated in vacuo. The residue was purified by flash column chromatography on silica gel (dichloromethane/methanol=50:1) to afford the desired product (220 mg, 18% yield). ESI-MS m/z: 472.3[M+H]+.

Workup

  1. temperatureat reflux for 2 h
  2. stirringthe resulting mixture was stirred at 60° C. for 16 h
  3. custompartitioned between NH4Cl aqueous solution and ethyl acetate
  4. washThe organic layer was washed with water and brine
  5. dry with materialdried over Na2SO4
  6. concentrationconcentrated in vacuo
  7. customThe residue was purified by flash column chromatography on silica gel (dichloromethane/methanol=50:1)

Sources & evidence

ORD record
ord-def786089cf4443dbb68a35043d10dd9
Source dataset
uspto-grants-2016_01
Patent number
US09227978B2

Reaction notes

Loading…