Phosgene → 5-Fluoro-1,2,3,4-tetrahydro4-[(pyrrolidino)carbonyl]quinoxalin-2-one

HRID 1736718Notes

Reaction equation

HRID 1736718 reaction equation
[F:1][C:2]1[CH:11]=[CH:10][CH:9]=[C:8]2[C:3]=1[NH:4][CH2:5][C:6](=[O:12])[NH:7]2.[CH:13]([N:16]([CH:19]([CH3:21])C)[CH2:17]C)([CH3:15])C.C1C[O:25]CC1.C(Cl)(Cl)=O>C1(C)C=CC=CC=1>[F:1][C:2]1[CH:11]=[CH:10][CH:9]=[C:8]2[C:3]=1[N:4]([C:17]([N:16]1[CH2:13][CH2:15][CH2:21][CH2:19]1)=[O:25])[CH2:5][C:6](=[O:12])[NH:7]2

Participants

6

Reactant 4

HCID 6371PhosgeneHCID 8028TetrahydrofuranHCID 81531DiisopropylethylamineHCID 229128785-Fluoro-1,2,3,4-tetrahydroquinoxalin-2-one

Product 1

HCID 229128415-Fluoro-1,2,3,4-tetrahydro4-[(pyrrolidino)carbonyl]quinoxalin-2-one

Reagents, catalysts & solvents 1

HCID 1140TolueneSolvent

Procedure

To 1.20 g of 5-fluoro-1,2,3,4-tetrahydroquinoxalin-2-one (EXAMPLE 24), 1.26 ml of diisopropylethylamine, and 15 ml of THF at 0° is added 6.0 ml of 1.2M phosgene in toluene. The ice bath is removed and the reaction is stirred for 2 h, at which time an additional 0.2 ml of diisopropylethylamine and 1.0 ml of phosgene solution are added. After an hour, 1.26 ml of diisopropylethylamine and 0.60 ml of pyrrolidine are added and the reaction is stored in the freezer over the weekend. The reaction is then partitioned between ethyl acetate and aq. sodium bicarbonate and saline. The organic layers are dried over magnesium sulfate and concentrated and the crude product is chromatographed on silica gel (250 ml) using ethyl acetate/dichloromethane (30/70) to give 1.47 g of product. Recrystallization from ethyl acetate/ethyl ether/hexane gives product in two crops; mp 186.5°-187.5°; MS (m/z) at 263; IR (mineral oil) 1692, 1658, 1407, 1604, 1623 cm-1 ; NMR (CDCl3) 1.85, 3.28, 4.27, 6.68, 6.82, 7.04, 8.41 δ.

Workup

  1. customThe ice bath is removed
  2. additionare added
  3. waitAfter an hour
  4. addition1.26 ml of diisopropylethylamine and 0.60 ml of pyrrolidine are added
  5. customThe reaction is then partitioned between ethyl acetate and aq. sodium bicarbonate and saline
  6. dry with materialThe organic layers are dried over magnesium sulfate
  7. concentrationconcentrated
  8. customthe crude product is chromatographed on silica gel (250 ml)

Sources & evidence

ORD record
ord-a00826b290a9435480d6f66c7db17ecf
Source dataset
uspto-grants-1996_07
Patent number
US05541324

Reaction notes

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