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

HRID 1378776Notes

Reaction equation

HRID 1378776 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-061439f1d1f24e8d98a7678d26e8df03
Source dataset
uspto-grants-1997_09
Patent number
US05668282

Reaction notes

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