Phosphorus oxychloride → (S)-methyl 2-chloro-3-(2-methylpyrrolidin-1-yl)quinoxaline-6-carboxylate

HRID 1403416Notes

Reaction equation

HRID 1403416 reaction equation
[CH3:1][C@H:2]1[CH2:6][CH2:5][CH2:4][N:3]1[C:7]1[C:8](=O)[NH:9][C:10]2[C:15]([N:16]=1)=[CH:14][C:13]([C:17]([O:19][CH3:20])=[O:18])=[CH:12][CH:11]=2.P(Cl)(Cl)([Cl:24])=O>>[Cl:24][C:8]1[C:7]([N:3]2[CH2:4][CH2:5][CH2:6][C@@H:2]2[CH3:1])=[N:16][C:15]2[C:10](=[CH:11][CH:12]=[C:13]([C:17]([O:19][CH3:20])=[O:18])[CH:14]=2)[N:9]=1

Participants

3

Reactant 2

HCID 24813Phosphorus oxychlorideHCID 67041797(S)-methyl 3-(2-methylpyrrolidin-1-yl)-2-oxo-1,2-dihydroquinoxaline-6-carboxylate

Product 1

HCID 86670565(S)-methyl 2-chloro-3-(2-methylpyrrolidin-1-yl)quinoxaline-6-carboxylateYield 80%

Procedure

The solution of methyl 3-[(2S)-2-methylpyrrolidin-1-yl]-2-oxo-1,2-dihydroquinoxaline-6-carboxylate (5.9 g, 20.54 mmol,) in phosphorus oxychloride (100 mL) was stirred overnight at 120° C. in an oil bath. The reaction mixture was concentrated in vacuo and diluted with dichloromethane (500 mL) and ice-water (500 mL), adjusted to pH 7 with NaHCO3 solution. The solution was extracted with dichloromethane (3×200 mL) and the organic layers combined, dried over anhydrous sodium sulfate and concentrated in vacuo to give a residue, which was purified by silica gel column chromatography eluting with 2% ethyl acetate in petroleum ether to afford methyl 2-chloro-3-[(2S)-2-methylpyrrolidin-1-yl]quinoxaline-6-carboxylate as a yellow solid (5 g, 80%).

Workup

  1. concentrationThe reaction mixture was concentrated in vacuo
  2. additiondiluted with dichloromethane (500 mL) and ice-water (500 mL)
  3. extractionThe solution was extracted with dichloromethane (3×200 mL)
  4. dry with materialdried over anhydrous sodium sulfate
  5. concentrationconcentrated in vacuo
  6. customto give a residue, which
  7. customwas purified by silica gel column chromatography
  8. washeluting with 2% ethyl acetate in petroleum ether

Sources & evidence

ORD record
ord-1d4d31efe39a4965ae4bde1583fc58ae
Source dataset
uspto-grants-2014_12
Patent number
US08912188B2

Reaction notes

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