Diisopropylamine → N-methoxy-N-methyl-3-{2-cyclopropyl-4-(4-fluorophenyl)quinolin-3-yl}-3-hydroxypropanamide

HRID 1197640Notes

Reaction equation

HRID 1197640 reaction equation
C([Li])CCC.C(NC(C)C)(C)C.[CH3:13][O:14][N:15]([CH3:19])[C:16](=[O:18])[CH3:17].[CH:20]1([C:23]2[C:32]([CH:33]=[O:34])=[C:31]([C:35]3[CH:40]=[CH:39][C:38]([F:41])=[CH:37][CH:36]=3)[C:30]3[C:25](=[CH:26][CH:27]=[CH:28][CH:29]=3)[N:24]=2)[CH2:22][CH2:21]1>C1COCC1>[CH3:13][O:14][N:15]([CH3:19])[C:16](=[O:18])[CH2:17][CH:33]([C:32]1[C:23]([CH:20]2[CH2:21][CH2:22]2)=[N:24][C:25]2[C:30]([C:31]=1[C:35]1[CH:40]=[CH:39][C:38]([F:41])=[CH:37][CH:36]=1)=[CH:29][CH:28]=[CH:27][CH:26]=2)[OH:34]

Participants

6

Reactant 4

HCID 7912DiisopropylamineHCID 537505N-Methoxy-N-methylacetamideHCID 99479742-Cyclopropyl-4-(4-fluorophenyl)-3-quinolinecarboxaldehydeHCID 178418339Butyllithium

Product 1

HCID 18954750N-methoxy-N-methyl-3-{2-cyclopropyl-4-(4-fluorophenyl)quinolin-3-yl}-3-hydroxypropanamideYield 91.1%

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent3×

Procedure

Butyllithium (1.64M hexane solution, 7.54 ml, 12.4 mmol) was added to a THF (40 ml) solution of diisopropylamine (1.25 g, 12.4 mmol) at -78 ° C., and the mixture was stirred for 15 minutes. Thereto was added a THF (20 ml) solution of N-methoxy-N-methylacetamide (1.27 g, 12.3 mmol) at -78 ° C., and the resulting mixture was stirred at -78 ° C. for 15 minutes. To this mixture was added a THF (40 ml) solution of 2-cyclopropyl-4-(4-fluorophenyl)-3-formylquinoline (3.00 g, 10.3 mmol). The reaction mixture was stirred at -78 ° C. to room temperature over a period of 3 hours before quenching with water and extraction with diethyl ether. The ethereal organic layer was washed with saturated sodium chloride aq solution, dried over magnesium sulfate, and concentrated in vacuo. The residue was purified by column chromatography (hexane:ethyl acetate=2:1) to give N-methoxy-N-methyl-3 -{2-cyclopropyl-4-(4-fluorophenyl)quinoline-3-yl}-3-hydroxypropanamide (3.70 g, 91% yield).

Workup

  1. stirringthe resulting mixture was stirred at -78 ° C. for 15 minutes
  2. stirringThe reaction mixture was stirred at -78 ° C. to room temperature over a period of 3 hours
  3. custombefore quenching with water and extraction with diethyl ether
  4. washThe ethereal organic layer was washed with saturated sodium chloride aq solution
  5. dry with materialdried over magnesium sulfate
  6. concentrationconcentrated in vacuo
  7. customThe residue was purified by column chromatography (hexane:ethyl acetate=2:1)

Sources & evidence

ORD record
ord-6b7077081fe44bf986ba39e7250ec26b
Source dataset
uspto-grants-1994_01
Patent number
US05276154

Reaction notes

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