Triethylamine → 6-chloro-N-{1-[3-(4-fluorophenoxy)propyl]-3-methoxy-4-piperidyl}-3,4-dihydro-4-methyl-3-oxo-2H-1,4-benzoxazine-8-carboxamide hydrochloride hemihydrate

HRID 329739Notes

Reaction equation

HRID 329739 reaction equation
[NH2:1][CH:2]1[CH2:7][CH2:6][N:5]([CH2:8][CH2:9][CH2:10][O:11][C:12]2[CH:17]=[CH:16][C:15]([F:18])=[CH:14][CH:13]=2)[CH2:4][CH:3]1[O:19][CH3:20].C(N(CC)CC)C.[Cl:28][C:29]1[CH:30]=[C:31]([C:41](Cl)=[O:42])[C:32]2[O:37][CH2:36][C:35](=[O:38])[N:34]([CH3:39])[C:33]=2[CH:40]=1>C(Cl)(Cl)Cl>[OH2:11].[ClH:28].[Cl:28][C:29]1[CH:30]=[C:31]([C:41]([NH:1][CH:2]2[CH2:7][CH2:6][N:5]([CH2:8][CH2:9][CH2:10][O:11][C:12]3[CH:13]=[CH:14][C:15]([F:18])=[CH:16][CH:17]=3)[CH2:4][CH:3]2[O:19][CH3:20])=[O:42])[C:32]2[O:37][CH2:36][C:35](=[O:38])[N:34]([CH3:39])[C:33]=2[CH:40]=1.[Cl:28][C:29]1[CH:30]=[C:31]([C:41]([NH:1][CH:2]2[CH2:7][CH2:6][N:5]([CH2:8][CH2:9][CH2:10][O:11][C:12]3[CH:13]=[CH:14][C:15]([F:18])=[CH:16][CH:17]=3)[CH2:4][CH:3]2[O:19][CH3:20])=[O:42])[C:32]2[O:37][CH2:36][C:35](=[O:38])[N:34]([CH3:39])[C:33]=2[CH:40]=1.[ClH:28]

Participants

5

Reactant 3

HCID 8471TriethylamineHCID 136778321-(3-(4-Fluorophenoxy)propyl)-3-methoxypiperidin-4-amineHCID 299420066-Chloro-4-methyl-3-oxo-3,4-dihydro-2H-1,4-benzoxazine-8-carbonyl chloride

Product 1

HCID 1317162386-chloro-N-{1-[3-(4-fluorophenoxy)propyl]-3-methoxy-4-piperidyl}-3,4-dihydro-4-methyl-3-oxo-2H-1,4-benzoxazine-8-carboxamide hydrochloride hemihydrate

Reagents, catalysts & solvents 1

HCID 6212ChloroformSolvent2×

Procedure

To a solution of 1.2 g of 4-amino-1-[3-(4-fluorophenoxy)propyl]-3-methoxypiperidine and 1.2 g of triethylamine in 50 ml of chloroform is added a solution of 2.5 g of 6-chloro-3,4-dihydro-4-methyl-3-oxo-2H-1,4-benzoxazine-8-carboxylic acid chloride in 10 ml of chloroform under cooling and stirring followed by stirring at room temperature for 4 hours. The resultant solution is washed with water, aqueous sodium hydrogen carbonate and then water, and dried over magnesium sulfate. After the solvent is distilled off under reduced pressure, the residue is purified by chromatography on silica gel using chloroform as an eluent, recrystallized from ethanol and treated with ethanolic hydrochloric acid to give 6-chloro-N-{1-[3-(4-fluorophenoxy)propyl]-3-methoxy-4-piperidyl}-3,4-dihydro-4-methyl-3-oxo-2H-1,4-benzoxazine-8-carboxamide hydrochloride hemihydrate, melting at 230° C. with decomposition.

Workup

  1. temperatureunder cooling
  2. stirringby stirring at room temperature for 4 hours
  3. washThe resultant solution is washed with water, aqueous sodium hydrogen carbonate
  4. dry with materialwater, and dried over magnesium sulfate
  5. distillationAfter the solvent is distilled off under reduced pressure
  6. customthe residue is purified by chromatography on silica gel
  7. customrecrystallized from ethanol
  8. additiontreated with ethanolic hydrochloric acid

Sources & evidence

ORD record
ord-b1132a501cf940ff9792e2c2591aa29f
Source dataset
uspto-grants-1990_01
Patent number
US04892872

Reaction notes

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