Hydrochloric Acid → 2-[3-(4-benzylpiperidin-1-yl)-propyl]-2H-1,4-benzoxazine-3(4H)-one

HRID 1974471Notes

Reaction equation

HRID 1974471 reaction equation
Br[CH2:2][CH2:3][CH2:4][CH:5]1[C:10](=[O:11])[NH:9][C:8]2[CH:12]=[CH:13][CH:14]=[CH:15][C:7]=2[O:6]1.NC1C=CC=CC=1O.BrC(CCCBr)C(Br)=O.[CH2:33]([CH:40]1[CH2:45][CH2:44][NH:43][CH2:42][CH2:41]1)[C:34]1[CH:39]=[CH:38][CH:37]=[CH:36][CH:35]=1.Cl>C1(C)C=CC=CC=1.C(N(CC)CC)C>[CH2:33]([CH:40]1[CH2:45][CH2:44][N:43]([CH2:2][CH2:3][CH2:4][CH:5]2[C:10](=[O:11])[NH:9][C:8]3[CH:12]=[CH:13][CH:14]=[CH:15][C:7]=3[O:6]2)[CH2:42][CH2:41]1)[C:34]1[CH:39]=[CH:38][CH:37]=[CH:36][CH:35]=1

Participants

8

Reactant 5

HCID 313Hydrochloric AcidHCID 58012-AminophenolHCID 317384-BenzylpiperidineHCID 111630822,5-dibromopentanoyl BromideHCID 143046582-(3-bromopropyl)-2H-1,4-benzoxazine-3(4H)-one

Product 1

HCID 150279152-[3-(4-benzylpiperidin-1-yl)-propyl]-2H-1,4-benzoxazine-3(4H)-one

Reagents, catalysts & solvents 2

HCID 1140TolueneSolventHCID 8471TriethylamineSolvent

Procedure

5.6 g (=0.02 m) of 2-(3-bromopropyl)-2H-1,4-benzoxazine-3(4H)-one prepared analogously to Example 1B starting from 2-aminophenol and 2,5-dibromopentanoyl bromide, 3.86 g (=0.022 m) of 4-benzylpiperidine, and 4.05 g of triethylamine were successively introduced into 70 ml of toluene. The reaction mixture was heated at reflux for 7 hours with stirring. To work up the reaction mixture it was cooled, and 100 ml of aqueous 20% strength hydrochloric acid solution were added. An oily paste was formed which was separated, washed with toluene, and then suspended in a mixture of aqueous sodium bicarbonate solution and dichloromethane. The organic phase was separated, dried over sodium sulfate, and then the solvent was distilled off. The remaining oily residue was fractionated by column chromatography. The title compound obtained in this way was crystallized from 15 ml of ethyl acetate. 6 g of 2-[3-(4-benzylpiperidin-1-yl)-propyl]-2H-1,4-benzoxazine-3(4H)-one were obtained as white crystals having a melting point of 108° C.

Workup

  1. temperatureThe reaction mixture was heated
  2. temperatureat reflux for 7 hours
  3. temperaturewas cooled
  4. customAn oily paste was formed which
  5. customwas separated
  6. washwashed with toluene
  7. additionsuspended in a mixture of aqueous sodium bicarbonate solution and dichloromethane
  8. customThe organic phase was separated
  9. dry with materialdried over sodium sulfate
  10. distillationthe solvent was distilled off

Sources & evidence

ORD record
ord-29d724bbac01484490c24ad2a4686a96
Source dataset
uspto-grants-1994_02
Patent number
US05283243

Reaction notes

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