3,4-Dihydro-2H-1,4-benzoxazine → 4-(2H-benzo[b][1,4]oxazin-4(3H)-yl)-3-methoxybenzonitrile

HRID 528642Notes

Reaction equation

HRID 528642 reaction equation
[O:1]1[CH2:6][CH2:5][NH:4][C:3]2[CH:7]=[CH:8][CH:9]=[CH:10][C:2]1=2.Br[C:12]1[CH:19]=[CH:18][C:15]([C:16]#[N:17])=[CH:14][C:13]=1[O:20][CH3:21].CC1(C)C2C(=C(P(C3C=CC=CC=3)C3C=CC=CC=3)C=CC=2)OC2C(P(C3C=CC=CC=3)C3C=CC=CC=3)=CC=CC1=2.CC(C)([O-])C.[Na+]>C1(C)C=CC=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.C1C=CC(/C=C/C(/C=C/C2C=CC=CC=2)=O)=CC=1.[Pd].[Pd]>[O:1]1[CH2:6][CH2:5][N:4]([C:12]2[CH:19]=[CH:18][C:15]([C:16]#[N:17])=[CH:14][C:13]=2[O:20][CH3:21])[C:3]2[CH:7]=[CH:8][CH:9]=[CH:10][C:2]1=2

Participants

7

Reactant 4

HCID 5850963,4-Dihydro-2H-1,4-benzoxazineHCID 6360441,1'-(9,9-Dimethyl-9H-xanthene-4,5-diyl)bis(1,1-diphenylphosphine)HCID 225911814-Bromo-3-methoxybenzonitrileHCID 23676156Sodium t-butoxide

Product 1

HCID 897616814-(2H-benzo[b][1,4]oxazin-4(3H)-yl)-3-methoxybenzonitrileYield 80.4%

Reagents, catalysts & solvents 2

HCID 9811564Bis(dibenzylideneacetone)palladiumCatalystHCID 1140TolueneSolvent

Conditions

Temperature
100 °C

Procedure

A mixture of 3,4-dihydro-2H-benzo[b][1,4]oxazine (500 mg, 3.69 mmol), 4-bromo-3-methoxybenzonitrile (784 mg, 3.69 mmol), Pd2(dba)3 (271 mg, 0.295 mmol), Xantphos (342 mg, 0.591 mmol) and sodium-tert-butoxide (590 mg, 6.14 mmol) in toluene (10 mL) was degassed for 10 minutes. The reaction mixture was heated at 100° C. for 1 h under microwave conditions. After completion, the reaction mixture was diluted with water (10 mL) and extracted with ethyl acetate (3×15 mL). The organic layer was dried over sodium sulfate and concentrated under reduced pressure to obtain the crude material which was purified by combi flash column chromatography (column size: 24 g; elution: 5% ethyl acetate in hexane) to obtain 4-(2H-benzo[b][1,4]oxazin-4(3H)-yl)-3-methoxybenzonitrile (790 mg, 80.2%) as yellow solid. m/z (ESI) 266.0 (M+H)+.

Workup

  1. customwas degassed for 10 minutes
  2. additionAfter completion, the reaction mixture was diluted with water (10 mL)
  3. extractionextracted with ethyl acetate (3×15 mL)
  4. dry with materialThe organic layer was dried over sodium sulfate
  5. concentrationconcentrated under reduced pressure
  6. customto obtain the crude material which
  7. customwas purified by combi flash column chromatography (column size: 24 g; elution: 5% ethyl acetate in hexane)

Sources & evidence

ORD record
ord-c0f1525d5df44c8b954ec8d6572f64ca
Source dataset
uspto-grants-2016_05
Patent number
US09346798B2

Reaction notes

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