tert-Butyl carbazate → tert-Butyl (3SR,5SR)-3-(2-chloro-4-fluorophenyl)-5-hydroxy-2-oxopiperidin-1-ylcarbamate

HRID 451520Notes

Reaction equation

HRID 451520 reaction equation
[Cl:1][C:2]1[CH:7]=[C:6]([F:8])[CH:5]=[CH:4][C:3]=1[CH:9]([CH2:14][CH:15]1[CH2:17][O:16]1)[C:10]([O:12]C)=O.[C:18]([O:22][C:23]([CH3:26])([CH3:25])[CH3:24])(=[O:21])[NH:19][NH2:20]>CC(O)C.C(OC(=O)C)C>[Cl:1][C:2]1[CH:7]=[C:6]([F:8])[CH:5]=[CH:4][C:3]=1[CH:9]1[CH2:14][CH:15]([OH:16])[CH2:17][N:20]([NH:19][C:18](=[O:21])[O:22][C:23]([CH3:26])([CH3:25])[CH3:24])[C:10]1=[O:12]

Participants

5

Reactant 2

HCID 70091tert-Butyl carbazateHCID 86656715Methyl 2-(2-chloro-4-fluorophenyl)-3-(oxiran-2-yl)propanoate

Product 1

HCID 86656716tert-Butyl (3SR,5SR)-3-(2-chloro-4-fluorophenyl)-5-hydroxy-2-oxopiperidin-1-ylcarbamate

Reagents, catalysts & solvents 2

HCID 3776IsopropanolSolventHCID 8857Ethyl AcetateSolvent

Procedure

To a solution of methyl 2-(2-chloro-4-fluorophenyl)-3-(oxiran-2-yl)propanoate (4.56 g, 17.6 mmol) in 2-propanol (20 mL) was added tert-butyl carbazate (2.3 g, 17.6 mmol) and the reaction heated to reflux for 16 hours. The reaction was then concentrated to dryness, redissolved in toluene (20 mL) and 1,5,7-triazobicylo(4.4.0)dec-5-ene (0.6 g, 4.4 mmol) was added and the mixture heated to reflux for 3 hours. The reaction was then diluted with ethylacetate, washed with 1 N HCl, dried with sodium sulfate and the solvent was evaporated in vacuo. The residue was recystallised from hot ethyl acetate to afford the title compound was obtained as a colourless solid (1.7 g, 26%). The mother liquor contained the trans isomer.

Workup

  1. temperaturethe reaction heated
  2. temperatureto reflux for 16 hours
  3. concentrationThe reaction was then concentrated to dryness
  4. dissolutionredissolved in toluene (20 mL)
  5. temperaturethe mixture heated
  6. temperatureto reflux for 3 hours
  7. washwashed with 1 N HCl
  8. dry with materialdried with sodium sulfate
  9. customthe solvent was evaporated in vacuo

Sources & evidence

ORD record
ord-e91b4cd99699447da4043544fdaf4c43
Source dataset
uspto-grants-2013_07
Patent number
US08486967B2

Reaction notes

Loading…