Boron trifluoride etherate → 1-Tert-Butyl 4-Ethyl 3-Oxoazepane-1,4-Dicarboxylate(WX618505)

HRID 1917258Notes

Reaction equation

HRID 1917258 reaction equation
[C:1]([O:5][C:6]([N:8]1[CH2:13][CH2:12][CH2:11][C:10](=[O:14])[CH2:9]1)=[O:7])([CH3:4])([CH3:3])[CH3:2].B(F)(F)F.CCOCC.[N+](=[CH:26][C:27]([O:29][CH2:30][CH3:31])=[O:28])=[N-].C([O-])(O)=O.[Na+]>CCOCC>[CH2:30]([O:29][C:27]([CH:26]1[CH2:11][CH2:12][CH2:13][N:8]([C:6]([O:5][C:1]([CH3:4])([CH3:3])[CH3:2])=[O:7])[CH2:9][C:10]1=[O:14])=[O:28])[CH3:31]

Participants

6

Reactant 4

HCID 8000Boron trifluoride etherateHCID 12192Ethyl diazoacetateHCID 516892Sodium BicarbonateHCID 2756825Tert-butyl 3-oxopiperidine-1-carboxylate

Product 1

HCID 574799101-Tert-Butyl 4-Ethyl 3-Oxoazepane-1,4-Dicarboxylate(WX618505)Yield 34%

Reagents, catalysts & solvents 1

HCID 3283Diethyl EtherSolvent

Procedure

To a 0° C. solution of 3-oxo-piperidine-1-carboxylic acid tert-butyl ester (11.3 g, 56.7 mmol) in Et2O (170 mL) was added BF3.Et2O (7.2 mL, 56.7 mmol) and ethyl diazoacetate (7.2 mL, 68.0 mmol) dropwise over 30 min. After an additional 1 h, satd. aq. NaHCO3 was added and the solution was stirred for 1 h, then was extracted with Et2O (2×). The combined organic layers were washed with brine, dried and concentrated. The resulting residue was purified via SiO2 chromatography (10-30% EtOAc/hexanes) to give 5.48 g (34%) of 3-oxo-azepane-1,4-dicarboxylic acid 1-tert-butyl ester 4-ethyl ester. In addition, 5.25 g (32%) of the more polar 4-oxo-azepane-1,3-dicarboxylic acid 1-tert-butyl ester 3-ethyl ester was isolated.

Workup

  1. extractionwas extracted with Et2O (2×)
  2. washThe combined organic layers were washed with brine
  3. customdried
  4. concentrationconcentrated
  5. customThe resulting residue was purified via SiO2 chromatography (10-30% EtOAc/hexanes)

Sources & evidence

ORD record
ord-91f4e5644eb742edb34937c6fbfbe0aa
Source dataset
uspto-grants-2013_12
Patent number
US08618288B2

Reaction notes

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