Piperazine → 4-(4-chloro-benzenesulfonyl)-6-methyl-8-piperazin-1-yl-3,4-dihydro-2H-benzo[1,4]oxazine

HRID 388285Notes

Reaction equation

HRID 388285 reaction equation
CC(C)([O-])C.[Na+].Br[C:8]1[C:17]2[O:16][CH2:15][CH2:14][N:13]([S:18]([C:21]3[CH:26]=[CH:25][C:24]([Cl:27])=[CH:23][CH:22]=3)(=[O:20])=[O:19])[C:12]=2[CH:11]=[C:10]([CH3:28])[CH:9]=1.[NH:29]1[CH2:34][CH2:33][NH:32][CH2:31][CH2:30]1>C1(C)C=CC=CC=1.C(OCC)(=O)C.C1C=CC(/C=C/C(/C=C/C2C=CC=CC=2)=O)=CC=1.C1C=CC(/C=C/C(/C=C/C2C=CC=CC=2)=O)=CC=1.C1C=CC(/C=C/C(/C=C/C2C=CC=CC=2)=O)=CC=1.[Pd].[Pd].C1(P(C2C=CC=CC=2)C2C=CC3C(=CC=CC=3)C=2C2C3C(=CC=CC=3)C=CC=2P(C2C=CC=CC=2)C2C=CC=CC=2)C=CC=CC=1>[Cl:27][C:24]1[CH:25]=[CH:26][C:21]([S:18]([N:13]2[C:12]3[CH:11]=[C:10]([CH3:28])[CH:9]=[C:8]([N:29]4[CH2:34][CH2:33][NH:32][CH2:31][CH2:30]4)[C:17]=3[O:16][CH2:15][CH2:14]2)(=[O:20])=[O:19])=[CH:22][CH:23]=1

Participants

8

Reactant 3

HCID 4837PiperazineHCID 225572608-bromo-4-(4-chloro-benzenesulfonyl)-6-methyl-3,4-dihydro-2H-benzo[1,4]oxazineHCID 23676156Sodium t-butoxide

Product 1

HCID 103867114-(4-chloro-benzenesulfonyl)-6-methyl-8-piperazin-1-yl-3,4-dihydro-2H-benzo[1,4]oxazineYield 79.9%

Reagents, catalysts & solvents 4

HCID 634876Binap, (A+-)-CatalystHCID 9811564Bis(dibenzylideneacetone)palladiumCatalystHCID 1140TolueneSolventHCID 8857Ethyl AcetateSolvent

Conditions

Temperature
95 °C

Procedure

A three neck flask was charged with tris(dibenzylideneacetone)dipalladium(0) (9.1 mg, 0.001 mmol, 2 mol % Pd), (±)-2,2′-bis(diphenylphosphino)-1,1′-binaphthyl (15.5 mg, 0.025 mmol, 5 mol %), and sodium-tert-butoxide (67 mg, 0.7 mmol) and flushed with nitrogen. A solution of 8-bromo-4-(4-chloro-benzenesulfonyl)-6-methyl-3,4-dihydro-2H-benzo[1,4]oxazine (201 mg, 0.5 mmol) and piperazine (129 mg, 1.5 mmol) in toluene (5 mL) was added. The mixture was heated to 95° C. and stirred for 18 hours. The mixture was cooled to room temperature, taken up in ethyl acetate and filtered. The organic phase was washed with water (2×20 mL) and extracted into 10% aqueous HCl (2×20 mL). The combined aqueous extracts were basified with solid potassium carbonate and extracted into ethyl acetate (2×20 mL). The combined organic extract was dried (K2CO3), filtered and concentrated to give the title compound as an oil (163 mg, 79.6%). The hydrochloride salt was prepared from ethanol-hydrogen chloride. MS: MH+=408. M.p. 147.9-152.9° C.

Workup

  1. customflushed with nitrogen
  2. temperatureThe mixture was cooled to room temperature
  3. filtrationfiltered
  4. washThe organic phase was washed with water (2×20 mL)
  5. extractionextracted into 10% aqueous HCl (2×20 mL)
  6. extractionextracted into ethyl acetate (2×20 mL)
  7. extractionThe combined organic extract
  8. dry with materialwas dried (K2CO3)
  9. filtrationfiltered
  10. concentrationconcentrated

Sources & evidence

ORD record
ord-ccd4fa356f9840229c1a170e318dd0e2
Source dataset
uspto-grants-2013_02
Patent number
US08377931B2

Reaction notes

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