Ethyl chloroformate → 6-chloro-3,4-dihydro-3-oxo-N-[1-(2-phenylethyl)-4-piperidyl]-2H-1,4-benzoxazine-8-carboxamide

HRID 329728

Reaction equation

HRID 329728 reaction equation
[Cl:1][C:2]1[CH:3]=[C:4]([C:13]([OH:15])=O)[C:5]2[O:10][CH2:9][C:8](=[O:11])[NH:7][C:6]=2[CH:12]=1.C(Cl)(=O)OCC.[NH2:22][CH:23]1[CH2:28][CH2:27][N:26]([CH2:29][CH2:30][C:31]2[CH:36]=[CH:35][CH:34]=[CH:33][CH:32]=2)[CH2:25][CH2:24]1.C(=O)([O-])O.[Na+]>O1CCCC1.CN(C)C=O.C(OCC)(=O)C.C(N(CC)CC)C>[Cl:1][C:2]1[CH:3]=[C:4]([C:13]([NH:22][CH:23]2[CH2:28][CH2:27][N:26]([CH2:29][CH2:30][C:31]3[CH:36]=[CH:35][CH:34]=[CH:33][CH:32]=3)[CH2:25][CH2:24]2)=[O:15])[C:5]2[O:10][CH2:9][C:8](=[O:11])[NH:7][C:6]=2[CH:12]=1

Participants

9

Reactant 4

HCID 10928Ethyl chloroformateHCID 516892Sodium BicarbonateHCID 107287881-(2-Phenylethyl)piperidin-4-amineHCID 147198366-Chloro-3-oxo-3,4-dihydro-2H-1,4-benzoxazine-8-carboxylic acid

Product 1

HCID 147198426-chloro-3,4-dihydro-3-oxo-N-[1-(2-phenylethyl)-4-piperidyl]-2H-1,4-benzoxazine-8-carboxamide

Reagents, catalysts & solvents 4

HCID 6228DimethylformamideSolventHCID 8028TetrahydrofuranSolventHCID 8471TriethylamineSolventHCID 8857Ethyl AcetateSolvent

Procedure

A solution of 4.56 g of 6-chloro-3,4-dihydro-3-oxo-2H-1,4-benzoxazine-8-carboxylic acid in 100 ml of tetrahydrofuran and 10 ml of dimethylformamide is cooled to below 0° C. and 2.2 ml of triethylamine is added under stirring thereto. Further, 2.3 g of ethyl chlorocarbonate is added and the mixture is stirred at a temperature below 5° C. for an hour. To the resultant mixture is added 4.2 g of 4-amino-1-(2-phenylethyl)piperidine and the mixture stirred for 4 hours. After completion of the reaction, aqueous sodium hydrogen carbonate and ethyl acetate are added. The organic layer is separated, washed with water and dried over magnesium sulfate. The solvent is distilled off and the residue is recrystallized from ethyl acetate-ethanol to give 6-chloro-3,4-dihydro-3-oxo-N-[1-(2-phenylethyl)-4-piperidyl]-2H-1,4-benzoxazine-8-carboxamide, melting at 233°-235° C.

Workup

  1. stirringthe mixture is stirred at a temperature below 5° C. for an hour
  2. stirringthe mixture stirred for 4 hours
  3. additionare added
  4. customThe organic layer is separated
  5. washwashed with water
  6. dry with materialdried over magnesium sulfate
  7. distillationThe solvent is distilled off
  8. customthe residue is recrystallized from ethyl acetate-ethanol

Sources & evidence

ORD record
ord-0d12e930f8274abcb8b38029358f07eb
Source dataset
uspto-grants-1990_01
Patent number
US04892872

Linked notes

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