tert-Butyl piperazine-1-carboxylate → HCID 69063356, compound

HRID 388286Notes

Reaction equation

HRID 388286 reaction equation
CC(C)([O-])C.[Na+].[C:7]1([S:13]([N:16]2[C:21]3[CH:22]=[C:23]([Cl:27])[CH:24]=[C:25](Br)[C:20]=3[O:19][CH2:18][CH2:17]2)(=[O:15])=[O:14])[CH:12]=[CH:11][CH:10]=[CH:9][CH:8]=1.[C:28]([O:32][C:33]([N:35]1[CH2:40][CH2:39][NH:38][CH2:37][CH2:36]1)=[O:34])([CH3:31])([CH3:30])[CH3:29]>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>[C:28]([O:32][C:33]([N:35]1[CH2:40][CH2:39][N:38]([C:25]2[C:20]3[O:19][CH2:18][CH2:17][N:16]([S:13]([C:7]4[CH:12]=[CH:11][CH:10]=[CH:9][CH:8]=4)(=[O:15])=[O:14])[C:21]=3[CH:22]=[C:23]([Cl:27])[CH:24]=2)[CH2:37][CH2:36]1)=[O:34])([CH3:31])([CH3:29])[CH3:30]

Participants

8

Reactant 3

HCID 143452tert-Butyl piperazine-1-carboxylateHCID 22557215HCID 22557215, compoundHCID 23676156Sodium t-butoxide

Product 1

HCID 69063356HCID 69063356, compoundYield 75%

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) (6.4 mg, 0.007 mmol, 2 mol % Pd), racemic-2,2′-bis(diphenylphosphino)-1,1′-binaphthyl (10.8 mg, 0.017 mmol, 5 mol %), and sodium tert-butoxide (47 mg, 0.48 mmol) and flushed with nitrogen. A solution of 4-benzenesulfonyl-8-bromo-6-chloro-3,4-dihydro-2H-benzo[1,4]oxazine (165 mg, 0.35 mmol) and piperazine-1-carboxylic acid tert-butyl ester (71.1 mg, 0.38 mmol) in toluene (2 mL) was added. The mixture was heated to 95° C. and stirred for 12 hours. The mixture was cooled to room temperature, taken up in ethyl acetate, filtered and concentrated. The crude material was purified by flash chromatography on silica gel (eluting with hexane-ethyl acetate; 7:3, v/v) to give 4-(4-Benzenesulfonyl-6-chloro-3,4-dihydro-2H-benzo[1,4]oxazin-8-yl)-piperazine-1-carboxylic acid tert-butyl ester as an oil (129 mg, 75%). MS: MH+=494. The crude material was dissolved in ethanol (1 mL) and was treated with a solution of 10% hydrogen chloride in ethanol (1 mL). The mixture was heated on a steam bath for 15 minutes. White crystals precipitated upon cooling to room temperature. The solid was collected, washed with cold ethanol. Drying under vacuum gave 4-benzenesulfonyl-6-chloro-8-piperazin-1-yl-3,4-dihydro-2H-benzo[1,4]oxazine, hydrochloride salt as a white powder (90 mg, 73%). MS: MH+=394. M.p. 202-205° C.

Workup

  1. customflushed with nitrogen
  2. temperatureThe mixture was cooled to room temperature
  3. filtrationfiltered
  4. concentrationconcentrated
  5. customThe crude material was purified by flash chromatography on silica gel (
  6. washeluting with hexane-ethyl acetate

Sources & evidence

ORD record
ord-41e974fdf3a24927a3244b64dcdc86a8
Source dataset
uspto-grants-2013_02
Patent number
US08377931B2

Reaction notes

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