1,1'-Carbonyldiimidazole → 6-chloro-4-(2-phenylethynyl)-4-(trifluoromethyl)-1H-3,1-benzoxazin-2-one

HRID 1376434Notes

Reaction equation

HRID 1376434 reaction equation
[NH2:1][C:2]1[CH:7]=[CH:6][C:5]([Cl:8])=[CH:4][C:3]=1[C:9]([OH:22])([C:14]#[C:15][C:16]1[CH:21]=[CH:20][CH:19]=[CH:18][CH:17]=1)[C:10]([F:13])([F:12])[F:11].[C:23](N1C=CN=C1)(N1C=CN=C1)=[O:24]>C1COCC1>[Cl:8][C:5]1[CH:6]=[CH:7][C:2]2[NH:1][C:23](=[O:24])[O:22][C:9]([C:14]#[C:15][C:16]3[CH:17]=[CH:18][CH:19]=[CH:20][CH:21]=3)([C:10]([F:13])([F:11])[F:12])[C:3]=2[CH:4]=1

Participants

4

Reactant 2

HCID 682631,1'-CarbonyldiimidazoleHCID 111209342-(2-Amino-5-chlorophenyl)-4-phenyl-1,1,1-trifluoro-3-butyn-2-ol

Product 1

HCID 4771206-chloro-4-(2-phenylethynyl)-4-(trifluoromethyl)-1H-3,1-benzoxazin-2-oneYield 40.8%

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent

Procedure

A solution of 2-(2-amino-5-chlorophenyl)-4-phenyl-1,1,1-trifluoro-3-butyn-2-ol (2.0 g, 6.1 mmol) and 11.0 g (12.0 mmol) of 1,1'-carbonyldiimidazole in 300 mL of dry THF was stirred under argon at 55° C. for 24 hours. The solvent was removed on a rotary evaporator and the residue was partitioned between 200 mL of ether and 400 mL of water. The layers were separated and the aqueous extracted once more with ether. The combined ether extracts were washed with 2×200 mL 10% citric acid and then with brine before drying over MgSO4. Removal of the drying agent and solvent provided 1.5 g (70%) of the crude title compound as an oil. Trimration with ether-hexane afforded 875 mg of (±) 6-chloro-4-phenylethynyl-4-trifluoromethyl-1,4-dihydro-2H-3,1-benzoxazin-2-one as a white solid, partial melt at 137°, clear at 147° C. 1H-NMR (CDCl3): δ6.92 (d, J=8 Hz, 1H), 7.30-7.49 (m, 4H), 7.58-7.65 (m, 3H), 8.99 (s, 1H).

Workup

  1. customThe solvent was removed on a rotary evaporator
  2. customthe residue was partitioned between 200 mL of ether and 400 mL of water
  3. customThe layers were separated
  4. extractionthe aqueous extracted once more with ether
  5. washThe combined ether extracts were washed with 2×200 mL 10% citric acid
  6. dry with materialwith brine before drying over MgSO4
  7. customRemoval of the drying agent and solvent
  8. customprovided 1.5 g (70%) of the crude title compound as an oil

Sources & evidence

ORD record
ord-1f4eb2dad6e74d6f8f8d2970888ba0fe
Source dataset
uspto-grants-1997_09
Patent number
US05663169

Reaction notes

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