Phosgene → 6-Fluoro-1,2,3,4-tetrahydro-3,3-dimethyl-4-[(pyrrolidino)carbonyl]quinoxalin-2-one

HRID 1736688Notes

Reaction equation

HRID 1736688 reaction equation
[C:1](Cl)(Cl)=[O:2].[F:5][C:6]1[CH:7]=[C:8]2[C:13](=[CH:14][CH:15]=1)[NH:12][C:11](=[O:16])[C:10]([CH3:18])([CH3:17])[NH:9]2.[CH:19]([N:22]([CH:25]([CH3:27])C)CC)([CH3:21])C.C1COCC1>C1(C)C=CC=CC=1>[F:5][C:6]1[CH:7]=[C:8]2[C:13](=[CH:14][CH:15]=1)[NH:12][C:11](=[O:16])[C:10]([CH3:18])([CH3:17])[N:9]2[C:1]([N:22]1[CH2:19][CH2:21][CH2:27][CH2:25]1)=[O:2]

Participants

6

Reactant 4

HCID 6371Phosgene2×HCID 8028TetrahydrofuranHCID 81531DiisopropylethylamineHCID 229128926-Fluoro-3,3-dimethyl-3,4-dihydro-1H-quinoxalin-2-one

Product 1

HCID 153912706-Fluoro-1,2,3,4-tetrahydro-3,3-dimethyl-4-[(pyrrolidino)carbonyl]quinoxalin-2-one

Reagents, catalysts & solvents 1

HCID 1140TolueneSolvent

Procedure

Phosgene in toluene (1.2M, 12.9 ml) is added to a mixture of 6-fluoro-1,2,3,4-tetrahydro-3,3-dimethylquinoxalin-2-one (IV, EXAMPLE 8, 1.001 g) and diisopropylethylamine (0.94 ml), and THF (10 ml) at 0°. After 45 min the reaction is allowed to warm to 20°-25°. After stirring for 3 hr, the reaction is again cooled to 0° and additional phosgene (4.2 ml) is added. The ice bath is removed and the reaction is stirred for 100 min, after which the excess phosgene and solvents are removed via a water aspirator. The mixture is then stirred with THF (10 ml) and of pyrrolidine (0.90 ml) are added. After stirring overnight, the reaction is concentrated mid the residue chromatographed on silica gel eluting with methanol/methylene chloride (2/98). The appropriate fractions are pooled and concentrated to give the title compound; MS (m/z) at 291; IR (mineral oil) 1681, 1660, 1396 and 1163 cm-1 ; NMR (CDCl3) 1.4-2.0, 3.15, 3.6, 6.43, 6.65, 6.76 and 8.32 δ.

Workup

  1. temperatureto warm to 20°-25°
  2. temperaturethe reaction is again cooled to 0°
  3. customThe ice bath is removed
  4. stirringthe reaction is stirred for 100 min
  5. customafter which the excess phosgene and solvents are removed via a water aspirator
  6. stirringThe mixture is then stirred with THF (10 ml) and of pyrrolidine (0.90 ml)
  7. additionare added
  8. stirringAfter stirring overnight
  9. concentrationthe reaction is concentrated mid the residue
  10. customchromatographed on silica gel eluting with methanol/methylene chloride (2/98)
  11. concentrationconcentrated

Sources & evidence

ORD record
ord-d5f3007ffcbb453e9d4119e35570b559
Source dataset
uspto-grants-1996_07
Patent number
US05541324

Reaction notes

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