Hydrochloric Acid → 8-Benzyl-6,7,8,9-tetrahydropyrazino[2,3-f][1,4]oxazepin-3-amine

HRID 2188680Notes

Reaction equation

HRID 2188680 reaction equation
[CH2:1]([N:8]1[CH2:14][C:13]2[N:15]=[CH:16][C:17](Cl)=[N:18][C:12]=2[O:11][CH2:10][CH2:9]1)[C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][CH:3]=1.C1(P(C2CCCCC2)C2C=CC=CC=2C2C=CC=CC=2)CCCCC1.C[Si](C)(C)[N-:47][Si](C)(C)C.[Li+].Cl.C(=O)([O-])O.[Na+]>C1COCC1.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]>[CH2:1]([N:8]1[CH2:14][C:13]2[N:15]=[CH:16][C:17]([NH2:47])=[N:18][C:12]=2[O:11][CH2:10][CH2:9]1)[C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][CH:3]=1

Participants

8

Reactant 5

HCID 313Hydrochloric AcidHCID 516892Sodium BicarbonateHCID 2733832Lithium HexamethyldisilazideHCID 27342162-(Dicyclohexylphosphino)biphenylHCID 866489818-Benzyl-3-chloro-6,7,8,9-tetrahydropyrazino[2,3-f][1,4]oxazepine

Product 1

HCID 669931398-Benzyl-6,7,8,9-tetrahydropyrazino[2,3-f][1,4]oxazepin-3-amineYield 49%

Reagents, catalysts & solvents 2

HCID 9811564Bis(dibenzylideneacetone)palladiumCatalystHCID 8028TetrahydrofuranSolvent

Procedure

To a solution of 8-benzyl-3-chloro-6,7,8,9-tetrahydropyrazino[2,3-f][1,4]oxazepine (213 mg) in THF (5 mL) were added 2-(dicyclohexylphosphino)biphenyl (19 mg), Pd2(dba)3 (21 mg) and lithium hexamethyl disilazide (1 M THF solution, 1.16 mL) under an argon stream at room temperature. The reaction mixture was stirred at 60° C. to 70° C. for 1.5 hr. The reaction mixture was cooled to room temperature, 1 N hydrochloric acid (10 mL) was added, and the mixture was stirred at room temperature for 10 min. The aqueous layer was basified with saturated aqueous sodium hydrogen carbonate, and extracted with ethyl acetate. The combined organic layer was washed with water and saturated brine, dried over magnesium sulfate, and concentrated. The residue was purified by basic silica gel column chromatography (solvent gradient: 20→100% ethyl acetate/hexane) to give the title compound (97 mg, 49%) as a pale-yellow solid.

Workup

  1. stirringthe mixture was stirred at room temperature for 10 min
  2. extractionextracted with ethyl acetate
  3. washThe combined organic layer was washed with water and saturated brine
  4. dry with materialdried over magnesium sulfate
  5. concentrationconcentrated
  6. customThe residue was purified by basic silica gel column chromatography (solvent gradient: 20→100% ethyl acetate/hexane)

Sources & evidence

ORD record
ord-54518bfcc7534fbdbd8f266994ca3da1
Source dataset
uspto-grants-2012_12
Patent number
US08324201B2

Reaction notes

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