2,3-Dichloropyridine → 4-(3-chloropyridin-2-yl)-3,4-dihydro-2H-1,4-benzoxazine

HRID 1661131Notes

Reaction equation

HRID 1661131 reaction equation
[O:1]1[C:6]2[CH:7]=[CH:8][CH:9]=[CH:10][C:5]=2[NH:4][CH2:3][CH2:2]1.[H-].[Na+].Cl[C:14]1[C:19]([Cl:20])=[CH:18][CH:17]=[CH:16][N:15]=1.O1C2C=CC=CC=2C=CN1>O1CCOCC1.C(OCC)(=O)C.C(O)(=O)C>[Cl:20][C:19]1[C:14]([N:4]2[C:5]3[CH:10]=[CH:9][CH:8]=[CH:7][C:6]=3[O:1][CH2:2][CH2:3]2)=[N:15][CH:16]=[CH:17][CH:18]=1

Participants

8

Reactant 4

HCID 169882,3-Dichloropyridine2×HCID 24758Sodium hydride2×HCID 5850963,4-Dihydro-2H-1,4-benzoxazineHCID 17845026Benzoxazines

Product 1

HCID 576132544-(3-chloropyridin-2-yl)-3,4-dihydro-2H-1,4-benzoxazineYield 46%

Reagents, catalysts & solvents 3

HCID 176Acetic AcidSolventHCID 8857Ethyl AcetateSolventHCID 312751,4-DioxaneSolvent

Procedure

To a solution of 3,4-dihydro-2H-1,4-benzoxazine (198 mg, 1-47 mmol) in dry dioxane (3 mL) was added 60% sodium hydride/mineral oil (90 mg, 2.25 mmol) and let stir at ambient temperature for 15 min. Then 2,3-dichloropyridine (264 mg, 1.78 mmol) was added and the mixture was warm to 80 C. Over 24 hours periodically added small portions (˜10 mg) of NaH and another 90 mg of 2,3-dichloropyridine until all of the benzoxazine was gone. Cooled and diluted with ethyl acetate, neutralized with acetic acid and then washed with NaHCO3 solution, followed with water. The organic layer was dried over anhydrous sodium sulfate, filtered, and the solvent evaporated. This residue was purified by chromatography on silica gel eluting with a 10-15% acetone/hexane gradient to give the title compound as a viscous oil which slowly solidified (168 mg, 46% yield). 1H-NMR (500 MHz, CDCl3): δ 8.35 (1H, d, J=4.6 Hz), 7.74 (1H, d, J=8.1 Hz), 7.05 (1H, dd, J=4.7, 8.0 Hz), 6.90 (1H, d, J=7.4 Hz), 6.83 (1H, t, J=7.3 Hz), 6.75 (1H, t, J=7.3 Hz), 6.55 (1H, d, J=7.8 Hz), 4.39 (2H, t, J=4.3), 3.84 (2H, t, J=4.Hz). m/e (m+1): 247.0

Workup

  1. temperaturethe mixture was warm to 80 C
  2. temperatureCooled
  3. washwashed with NaHCO3 solution
  4. dry with materialThe organic layer was dried over anhydrous sodium sulfate
  5. filtrationfiltered
  6. customthe solvent evaporated
  7. customThis residue was purified by chromatography on silica gel eluting with a 10-15% acetone/hexane gradient

Sources & evidence

ORD record
ord-d4a387faaa374ca2b45e7187192ba8db
Source dataset
uspto-grants-2011_10
Patent number
US08030332B2

Reaction notes

Loading…