Diethyl chlorophosphate → Ethyl 4,5-Dihydro-4,4-dimethylimidazo[1,5-a]quinoxaline-3-carboxylate

HRID 1736696Notes

Reaction equation

HRID 1736696 reaction equation
[CH3:1][C:2]([CH3:5])([O-])[CH3:3].[K+].C([N:15]1[C:24]2[C:19](=[CH:20][CH:21]=[CH:22][CH:23]=2)[NH:18][C:17](=O)C1)(=O)C1C=CC=CC=1.P(Cl)(OCC)(OCC)=O.[N+:35]([CH2:37][C:38]([O:40][CH2:41][CH3:42])=[O:39])#[C-]>C1COCC1>[CH3:1][C:2]1([CH3:5])[NH:15][C:24]2[C:19](=[CH:20][CH:21]=[CH:22][CH:23]=2)[N:18]2[CH:17]=[N:35][C:37]([C:38]([O:40][CH2:41][CH3:42])=[O:39])=[C:3]12

Participants

6

Reactant 4

HCID 13139Diethyl chlorophosphateHCID 533707Ethyl isocyanoacetateHCID 7343784-Benzoyl-1,2,3,4-tetrahydroquinoxalin-2-oneHCID 23665647Potassium tert-butoxide2×

Product 1

HCID 54175730Ethyl 4,5-Dihydro-4,4-dimethylimidazo[1,5-a]quinoxaline-3-carboxylate

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent

Procedure

Potassium tert-butoxide (1M, 4.54 ml) is added to 1,2,3,4-tetrahydro-3,3-dimethylquinoxalin-2-one (IV, EXAMPLE 2, 0.762 g) in THF (4 ml) at ice/saline temperature. The reaction is stirred for 40 min, at which time diethyl chlorophosphate (0.656 ml) is added. After stirring at ice-saline temperature for 2 hr, ethyl isocyanoacetate (0.562 g) is added, followed by potassium t-butoxide (1 M, 4.97 ml). The reaction is stirred for 3.5 hr, allowing it to slowly warm to 20°-25°. The reaction is then quenched with several drops of acetic acid and then partitioned between ethyl acetate, aqueous sodium bicarbonate and saline. The phases are separated and the organic phase is dried over magnesium sulfate, concentrated, and the resulting crude product chromatographed on silica gel (200 ml) eluting with methanol/dichloromethane (2/98). The appropriate fractions are pooled and concentrated to give the title compound, mp 145°-149°; NMR (CDCl3) 1.44, 1.74, 3.79, 4.40, 6.77, 6.82, 7.10, and 7.39 δ.

Workup

  1. additionis added
  2. stirringThe reaction is stirred for 3.5 hr
  3. temperatureto slowly warm to 20°-25°
  4. customThe reaction is then quenched with several drops of acetic acid
  5. custompartitioned between ethyl acetate, aqueous sodium bicarbonate and saline
  6. customThe phases are separated
  7. dry with materialthe organic phase is dried over magnesium sulfate
  8. concentrationconcentrated
  9. customthe resulting crude product chromatographed on silica gel (200 ml)
  10. washeluting with methanol/dichloromethane (2/98)
  11. concentrationconcentrated

Sources & evidence

ORD record
ord-59cae783fdfe4013a77bf35f574c5fad
Source dataset
uspto-grants-1996_07
Patent number
US05541324

Reaction notes

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