Tetrahydrofuran → 5-Cyclopropyl-6-(4-fluorophenyl)-2-isopropoxynicotinaldehyde

HRID 530997Notes

Reaction equation

HRID 530997 reaction equation
C1COCC1.[CH:6]1([C:9]2[C:10]([C:23]3[CH:28]=[CH:27][C:26]([F:29])=[CH:25][CH:24]=3)=[N:11][C:12]([O:19][CH:20]([CH3:22])[CH3:21])=[C:13]([CH:18]=2)[C:14](OC)=[O:15])[CH2:8][CH2:7]1.[H-].[Al+3].[Li+].[H-].[H-].[H-].[OH-].[Na+]>O>[CH:6]1([C:9]2[C:10]([C:23]3[CH:28]=[CH:27][C:26]([F:29])=[CH:25][CH:24]=3)=[N:11][C:12]([O:19][CH:20]([CH3:22])[CH3:21])=[C:13]([CH:18]=2)[CH:14]=[O:15])[CH2:8][CH2:7]1

Participants

6

Reactant 4

HCID 8028Tetrahydrofuran2×HCID 14798Sodium HydroxideHCID 21226445Aluminium lithium hydrideHCID 117992411Methyl 5-cyclopropyl-6-(4-fluorophenyl)-2-isopropoxynicotinate

Product 1

HCID 1179921695-Cyclopropyl-6-(4-fluorophenyl)-2-isopropoxynicotinaldehydeYield 85%

Reagents, catalysts & solvents 1

HCID 962WaterSolvent2×

Procedure

A THF (20 mL) solution of methyl 5-cyclopropyl-6-(4-fluorophenyl)-2-isopropoxynicotinate (3.17 g) was added to a THF (20 mL) suspension of lithium aluminum hydride (365 mg) under ice cooling in a nitrogen atmosphere. After stirring at the same temperature as above for 30 minutes, water (0.35 mL) and a 15% aqueous sodium hydroxide solution (0.35 mL) were added thereto, and the mixture was stirred for 5 minutes. Then, water (1.05 mL) was further added thereto. The reaction mixture was stirred for 30 minutes and then filtered. The filtrate was concentrated under reduced pressure. Manganese dioxide (8.36 g) was added to a toluene (30 mL) solution of the obtained residue, and the mixture was stirred at 60° C. for 1 hour in a nitrogen atmosphere. The reaction mixture was filtered, and then, the solvent was distilled off under reduced pressure. The obtained residue was purified by silica gel column chromatography (hexane/ethyl acetate) to obtain the title compound (2.45 g).

Workup

  1. stirringThe reaction mixture was stirred for 30 minutes
  2. filtrationfiltered
  3. concentrationThe filtrate was concentrated under reduced pressure
  4. additionManganese dioxide (8.36 g) was added to a toluene (30 mL) solution of the obtained residue
  5. stirringthe mixture was stirred at 60° C. for 1 hour in a nitrogen atmosphere
  6. filtrationThe reaction mixture was filtered
  7. distillationthe solvent was distilled off under reduced pressure
  8. customThe obtained residue was purified by silica gel column chromatography (hexane/ethyl acetate)

Sources & evidence

ORD record
ord-cb984f2907374e7ca43b83a9f06d7e66
Source dataset
uspto-grants-2016_05
Patent number
US09353108B2

Reaction notes

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