4-Methylmorpholine → 6-chloro-3,4-dihydro-2,4-dimethyl-3-oxo-N-[1-(3-phenylpropyl)-4-piperidyl]-2H-1,4-benzoxazine-8carboxamide hydrochloride

HRID 329733

Reaction equation

HRID 329733 reaction equation
[Cl:1][C:2]1[CH:3]=[C:4]([C:15]([OH:17])=O)[C:5]2[O:10][CH:9]([CH3:11])[C:8](=[O:12])[N:7]([CH3:13])[C:6]=2[CH:14]=1.C[N:19]1CCOCC1.C(Cl)(=O)OCC(C)C.N[CH:34]1[CH2:39][CH2:38][CH2:37][N:36]([CH2:40][CH2:41][CH2:42][C:43]2[CH:48]=[CH:47][CH:46]=[CH:45][CH:44]=2)[CH2:35]1.C(=O)([O-])O.[Na+]>O1CCCC1.C(OCC)(=O)C>[ClH:1].[Cl:1][C:2]1[CH:3]=[C:4]([C:15]([NH:19][CH:39]2[CH2:38][CH2:37][N:36]([CH2:40][CH2:41][CH2:42][C:43]3[CH:48]=[CH:47][CH:46]=[CH:45][CH:44]=3)[CH2:35][CH2:34]2)=[O:17])[C:5]2[O:10][CH:9]([CH3:11])[C:8](=[O:12])[N:7]([CH3:13])[C:6]=2[CH:14]=1

Participants

8

Reactant 5

HCID 79724-MethylmorpholineHCID 62365Isobutyl chloroformateHCID 516892Sodium BicarbonateHCID 145172346-chloro-3,4-dihydro-2,4-dimethyl-3-oxo-2H-1,4-benzoxazine-8-carboxylic acidHCID 198711523-Amino-1-(3-phenylpropyl)piperidine

Product 1

HCID 198711756-chloro-3,4-dihydro-2,4-dimethyl-3-oxo-N-[1-(3-phenylpropyl)-4-piperidyl]-2H-1,4-benzoxazine-8carboxamide hydrochloride

Reagents, catalysts & solvents 2

HCID 8028TetrahydrofuranSolventHCID 8857Ethyl AcetateSolvent

Procedure

A solution of 4.0 g of 6-chloro-3,4-dihydro-2,4-dimethyl-3-oxo-2H-1,4-benzoxazine-8-carboxylic acid in 80 ml of tetrahydrofuran is cooled to below 0° C. and 3.17 g of N-methylmorpholine is added under stirring thereto. Further, 2.35 g of isobutyl chlorocarbonate is added and the mixture is stirred at the same temperature for 45 minutes. To the resultant mixture is added 3.77 g of 3-amino-1-(3-phenylpropyl)piperidine and the mixture stirred for 3 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 ethanol followed by treating with ethnnolic hydrochloric acid to give 6-chloro-3,4-dihydro-2,4-dimethyl-3-oxo-N-[1-(3-phenylpropyl)-4-piperidyl]-2H-1,4-benzoxazine-8carboxamide hydrochloride, melting at 174°-176° C. with decomposition.

Workup

  1. stirringthe mixture is stirred at the same temperature for 45 minutes
  2. stirringthe mixture stirred for 3 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 ethanol
  9. additionby treating with ethnnolic hydrochloric acid

Sources & evidence

ORD record
ord-c4714057396c4404810cb3a5185f4383
Source dataset
uspto-grants-1990_01
Patent number
US04892872

Linked notes

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