Aluminium lithium hydride → [2-Pyridazin-4-yl-4-(trifluoromethyl)phenyl]methanol

HRID 509117Notes

Reaction equation

HRID 509117 reaction equation
[N:1]1[CH:6]=[CH:5][C:4]([C:7]2[CH:17]=[C:16]([C:18]([F:21])([F:20])[F:19])[CH:15]=[CH:14][C:8]=2[C:9](OCC)=[O:10])=[CH:3][N:2]=1.[H-].[Al+3].[Li+].[H-].[H-].[H-]>O1CCCC1>[N:1]1[CH:6]=[CH:5][C:4]([C:7]2[CH:17]=[C:16]([C:18]([F:20])([F:21])[F:19])[CH:15]=[CH:14][C:8]=2[CH2:9][OH:10])=[CH:3][N:2]=1

Participants

4

Reactant 2

HCID 21226445Aluminium lithium hydride2×HCID 68042663Ethyl 2-pyridazin-4-yl-4-(trifluoromethyl)benzoate

Product 1

HCID 66652718[2-Pyridazin-4-yl-4-(trifluoromethyl)phenyl]methanolYield 45.1%

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent

Conditions

Temperature
0 °C

Procedure

To a solution of ethyl 2-pyridazin-4-yl-4-(trifluoromethyl)benzoate (Preparation 31, 510 mg, 1.72 mmol) in tetrahydrofuran (15 mL) cooled to 0° C. was added lithium aluminium hydride (2.0 M in tetrahydrofuran, 0.86 mL, 1.72 mmol) dropwise. The reaction was stirred for 1 hour at 0° C. before warming to room temperature and stirring for a further 2 hours. The reaction was re-cooled to 0° C. before excess lithium aluminium hydride was quenched by the addition of water (65 μL), 2M aqueous solution of sodium hydroxide (130 μL) and further water (195 μL). Diethyl ether and anhydrous magnesium sulphate were added to aid the formation of a granular solid which was filtered. The organics were concentrated in vacuo and re-dissolved in dichloromethane (5 mL). The organics were purified by silica gel column chromatography (ISCO™ companion, 40 g column, eluting with 100% heptane to 100% ethyl acetate to 5% methanol in ethyl acetate). Fractions containing product were combined and concentrated in vacuo to obtain the title compound as a yellow solid (197 mg, 45%).

Workup

  1. temperaturebefore warming to room temperature
  2. stirringstirring for a further 2 hours
  3. customwas quenched by the addition of water (65 μL), 2M aqueous solution of sodium hydroxide (130 μL) and further water (195 μL)
  4. additionDiethyl ether and anhydrous magnesium sulphate were added
  5. filtrationwas filtered
  6. concentrationThe organics were concentrated in vacuo
  7. dissolutionre-dissolved in dichloromethane (5 mL)
  8. customThe organics were purified by silica gel column chromatography (ISCO™ companion, 40 g column, eluting with 100% heptane to 100% ethyl acetate to 5% methanol in ethyl acetate)
  9. additionFractions containing product
  10. concentrationconcentrated in vacuo

Sources & evidence

ORD record
ord-9c328dae1ea345ba9667b105941c9870
Source dataset
uspto-grants-2015_08
Patent number
US09096558B2

Reaction notes

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