Pyrrolidine → 1,1-Dimethylethyl 2,3-dihydro-9-(1-pyrrolidinyl)-1,4-benzoxazepine-4(5H)-carboxylate

HRID 886841Notes

Reaction equation

HRID 886841 reaction equation
Br[C:2]1[C:12]2[O:11][CH2:10][CH2:9][N:8]([C:13]([O:15][C:16]([CH3:19])([CH3:18])[CH3:17])=[O:14])[CH2:7][C:6]=2[CH:5]=[CH:4][CH:3]=1.[NH:20]1[CH2:24][CH2:23][CH2:22][CH2:21]1.CC(C1C=C(C(C)C)C(C2C=CC=CC=2P(C2CCCCC2)C2CCCCC2)=C(C(C)C)C=1)C.CC(C)([O-])C.[Na+]>O1CCOCC1.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].O>[N:20]1([C:2]2[C:12]3[O:11][CH2:10][CH2:9][N:8]([C:13]([O:15][C:16]([CH3:19])([CH3:18])[CH3:17])=[O:14])[CH2:7][C:6]=3[CH:5]=[CH:4][CH:3]=2)[CH2:24][CH2:23][CH2:22][CH2:21]1

Participants

8

Reactant 4

HCID 31268PyrrolidineHCID 111557942-Dicyclohexylphosphino-2',4',6'-triisoprophylbiphenylHCID 23676156Sodium t-butoxideHCID 59403519Tert-butyl 9-bromo-2,3-dihydrobenzo[F][1,4]oxazepine-4(5H)-carboxylate

Product 1

HCID 685786441,1-Dimethylethyl 2,3-dihydro-9-(1-pyrrolidinyl)-1,4-benzoxazepine-4(5H)-carboxylateYield 26.4%

Reagents, catalysts & solvents 3

HCID 9811564Bis(dibenzylideneacetone)palladiumCatalystHCID 962WaterSolventHCID 312751,4-DioxaneSolvent

Procedure

A solution of tert-butyl 9-bromo-2,3-dihydro-1,4-benzoxazepine-4(5H)-carboxylate (350 mg, 1.07 mmol), pyrrolidine (0.274 ml, 3.27 mmol), X-phos (30.5 mg, 0.064 mmol), tris(dibenzylideneacetone)dipalladium(0) (19.3 mg, 0.0212 mmol) and sodium tert-butoxide (154 mg, 1.60 mmol) in dioxane (7 ml) was stirred under an argon atmosphere for 2 hr at 80° C. The reaction mixture was poured into water, and the mixture was extracted with ethyl acetate. The extract was washed with water and dried over anhydrous magnesium sulfate. The solvent was evaporated under reduced pressure and the residue was purified by NH silica gel column chromatography (hexane:ethyl acetate=3:1) to give the desired product (90.0 mg, 26.4%) as an oil.

Workup

  1. extractionthe mixture was extracted with ethyl acetate
  2. washThe extract was washed with water
  3. dry with materialdried over anhydrous magnesium sulfate
  4. customThe solvent was evaporated under reduced pressure
  5. customthe residue was purified by NH silica gel column chromatography (hexane:ethyl acetate=3:1)

Sources & evidence

ORD record
ord-c5c9bea9923f4c888e205278ae092ba0
Source dataset
uspto-grants-2012_08
Patent number
US08247403B2

Reaction notes

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