Morpholine → 1,1-Dimethylethyl 2,3-dihydro-8-(4-morpholinyl)-1,4-benzoxazepine-4(5H)-carboxylate

HRID 886826Notes

Reaction equation

HRID 886826 reaction equation
Br[C:2]1[CH:19]=[CH:18][C:5]2[CH2:6][N:7]([C:11]([O:13][C:14]([CH3:17])([CH3:16])[CH3:15])=[O:12])[CH2:8][CH2:9][O:10][C:4]=2[CH:3]=1.[NH:20]1[CH2:25][CH2:24][O: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[CH:19]=[CH:18][C:5]3[CH2:6][N:7]([C:11]([O:13][C:14]([CH3:17])([CH3:16])[CH3:15])=[O:12])[CH2:8][CH2:9][O:10][C:4]=3[CH:3]=2)[CH2:25][CH2:24][O:23][CH2:22][CH2:21]1

Participants

8

Reactant 4

HCID 8083MorpholineHCID 111557942-Dicyclohexylphosphino-2',4',6'-triisoprophylbiphenylHCID 23676156Sodium t-butoxideHCID 68578192HCID 68578192, compound

Product 1

HCID 685784821,1-Dimethylethyl 2,3-dihydro-8-(4-morpholinyl)-1,4-benzoxazepine-4(5H)-carboxylateYield 49%

Reagents, catalysts & solvents 3

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

Procedure

A solution of tert-butyl 8-bromo-2,3-dihydro-1,4-benzoxazepine-4(5H)-carboxylate (100 mg, 0.305 mmol), morpholine (0.0292 ml, 0.335 mmol), X-phos (8.70 mg, 0.0182 mmol), tris(dibenzylideneacetone)dipalladium(0) (5.52 mg, 0.00604 mmol) and sodium tert-butoxide (43.8 mg, 0.456 mmol) in dioxane (2 ml) was stirred under an argon atmosphere for 7 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. The residue was purified by NH silica gel column chromatography (hexane:ethyl acetate=1:1) to give the desired product (50.0 mg, 49.0%) 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=1:1)

Sources & evidence

ORD record
ord-63e4c2e770df42e5b485215ed2d40530
Source dataset
uspto-grants-2012_08
Patent number
US08247403B2

Reaction notes

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