Dimethylformamide → Ethyl 8-chloro-1-cyclopropyl-7-fluoro-9-methyl-4-oxo-4H-quinolizine-3-carboxylate

HRID 1938827Notes

Reaction equation

HRID 1938827 reaction equation
O[C:2]1[C:3]([F:22])=[CH:4][N:5]2[C:10]([C:11]=1[CH3:12])=[C:9]([CH:13]1[CH2:15][CH2:14]1)[CH:8]=[C:7]([C:16]([O:18][CH2:19][CH3:20])=[O:17])[C:6]2=[O:21].CN(C=O)C.O=P(Cl)(Cl)[Cl:30]>C(Cl)Cl>[Cl:30][C:2]1[C:3]([F:22])=[CH:4][N:5]2[C:10]([C:11]=1[CH3:12])=[C:9]([CH:13]1[CH2:15][CH2:14]1)[CH:8]=[C:7]([C:16]([O:18][CH2:19][CH3:20])=[O:17])[C:6]2=[O:21]

Participants

5

Reactant 3

HCID 6228DimethylformamideHCID 24813Phosphorus oxychlorideHCID 178468608HCID 178468608, compound

Product 1

HCID 9927245Ethyl 8-chloro-1-cyclopropyl-7-fluoro-9-methyl-4-oxo-4H-quinolizine-3-carboxylateYield 80.3%

Reagents, catalysts & solvents 1

HCID 6344DichloromethaneSolvent

Procedure

Under nitrogen, ethyl 8-hydroxy-1-cyclopropyl-7-fluoro-9-methyl-4-oxo-4H-quinolizine-3-carboxylate (7A, 1.52 g, 5 mmol) was dissolved in methylene chloride (10 mL), and treated with DMF (0.73 g, 10 mmol) and POCl3 (1.53 g, 10 mmol). After stirring overnight, the mixture was poured into 10 mL of ice water. The organic layer was separated, and the aqueous layer was extracted with methylene chloride (10 mL×2). The organic layers were combined, washed with saturated NaHCO3 and brine, dried (MgSO4), filtered and concentrated to give the crude product which was chromatographed (silica gel, 50% ethyl acetate/hexane) to give the title compound (IIA, 1.3 g, 80%). 1H NMR (300 MHz, CDCl3): δ0.75 (m, 2H), 1.08 (m, 2H), 1.42 (t, 3H), 2.30 (m, 1H), 3.19 (s, 3H), 4.42 (q, 4H), 8.39 (s, 1H), 9.43 (d, 1H): MS (DCI/NH3) m/e 324 (M+H)+. Anal. Calcd for C16H15ClFNO3 : C, 59.35; H, 4.67; N, 4.32. Found C, 59.68; H, 4.76; N, 4.22.

Workup

  1. customThe organic layer was separated
  2. extractionthe aqueous layer was extracted with methylene chloride (10 mL×2)
  3. washwashed with saturated NaHCO3 and brine
  4. dry with materialdried (MgSO4)
  5. filtrationfiltered
  6. concentrationconcentrated
  7. customto give the crude product which
  8. customwas chromatographed (silica gel, 50% ethyl acetate/hexane)

Sources & evidence

ORD record
ord-9354dbec26dc4075b6df1e92efc8fa98
Source dataset
uspto-grants-1997_12
Patent number
US05693813

Reaction notes

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