Sodium hydride → ethyl 4-methyl-2-oxo-1-(tetrahydro-2H-pyran-4-yl)-7-(trifluoromethyl)-1,2-dihydroquinoline-3-carboxylate

HRID 242038Notes

Reaction equation

HRID 242038 reaction equation
[C:1]([C:4]1[CH:9]=[CH:8][C:7]([C:10]([F:13])([F:12])[F:11])=[CH:6][C:5]=1[N:14]([CH:23]1[CH2:28][CH2:27][O:26][CH2:25][CH2:24]1)[C:15](=[O:22])[CH2:16][C:17]([O:19][CH2:20][CH3:21])=[O:18])(=O)[CH3:2].[H-].[Na+]>C(O)C>[CH3:2][C:1]1[C:4]2[C:5](=[CH:6][C:7]([C:10]([F:13])([F:11])[F:12])=[CH:8][CH:9]=2)[N:14]([CH:23]2[CH2:28][CH2:27][O:26][CH2:25][CH2:24]2)[C:15](=[O:22])[C:16]=1[C:17]([O:19][CH2:20][CH3:21])=[O:18]

Participants

4

Reactant 2

HCID 24758Sodium hydrideHCID 66584554ethyl 3-((2-acetyl-5-(trifluoromethyl)phenyl)(tetrahydro-2H-pyran-4-yl)amino)-3-oxopropanoate

Product 1

HCID 66584514ethyl 4-methyl-2-oxo-1-(tetrahydro-2H-pyran-4-yl)-7-(trifluoromethyl)-1,2-dihydroquinoline-3-carboxylateYield 62.8%

Reagents, catalysts & solvents 1

HCID 702EthanolSolvent

Procedure

To a stirred solution of 550 mg (1.37 mmol) ethyl 3-((2-acetyl-5-(trifluoromethyl)phenyl)-(tetrahydro-2H-pyran-4-yl)amino)-3-oxopropanoate in ethanol (5 ml) was added 60 mg (1.51 mmol, 60% suspension in mineral oil) NaH at 0° C. The reaction mixture was stirred at RT for 30 min. Then the mixture was evaporated to dryness, the residue was diluted with water (10 ml) and acidified with 2N HCl to pH ˜3. The aq. part was extracted with ethyl acetate (3×10 ml). The combined organic layers were washed with water (10 ml), brine (10 ml), dried over anhydrous Na2SO4 and evaporated to get the crude which was again washed with sat. Na2CO3 to yield 330 mg (0.86 mmol, 62%) ethyl 4-methyl-2-oxo-1-(tetrahydro-2H-pyran-4-yl)-7-(trifluoromethyl)-1,2-dihydroquinoline-3-carboxylate which was used in the next step without further purification.

Workup

  1. customThen the mixture was evaporated to dryness
  2. additionthe residue was diluted with water (10 ml)
  3. extractionThe aq. part was extracted with ethyl acetate (3×10 ml)
  4. washThe combined organic layers were washed with water (10 ml), brine (10 ml)
  5. dry with materialdried over anhydrous Na2SO4
  6. customevaporated
  7. customto get the crude which
  8. washwas again washed with sat. Na2CO3

Sources & evidence

ORD record
ord-15549858d36c440bb3d03084017a66fa
Source dataset
uspto-grants-2014_02
Patent number
US08653102B2

Reaction notes

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