Aluminium lithium hydride → (S)-(2,4-difluoro-6-(pent-4-en-2-yloxy)phenyl)methanol

HRID 921125Notes

Reaction equation

HRID 921125 reaction equation
[F:1][C:2]1[CH:9]=[C:8]([F:10])[CH:7]=[C:6]([O:11][C@H:12]([CH2:14][CH:15]=[CH2:16])[CH3:13])[C:3]=1[CH:4]=[O:5].[H-].[Al+3].[Li+].[H-].[H-].[H-]>C1COCC1>[F:1][C:2]1[CH:9]=[C:8]([F:10])[CH:7]=[C:6]([O:11][C@H:12]([CH2:14][CH:15]=[CH2:16])[CH3:13])[C:3]=1[CH2:4][OH:5]

Participants

4

Reactant 2

HCID 21226445Aluminium lithium hydrideHCID 118307036(S)-2,4-difluoro-6-(pent-4-en-2-yloxy)benzaldehyde

Product 1

HCID 118307043(S)-(2,4-difluoro-6-(pent-4-en-2-yloxy)phenyl)methanolYield 39.3%

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent

Procedure

To a solution of (S)-2,4-difluoro-6-(pent-4-en-2-yloxy)benzaldehyde (0.3394 g, 1.500 mmol) in THF (4 ml) at 0° C. was added dropwise, lithium aluminum hydride (0.900 ml, 1.800 mmol). The resulting mixture was stirred at rt for 2 h. The mixture was cooled to 0° C. and quenched dropwise with brine then diluted with EtOAc and water. The organic phase was washed with brine, dried (Na2SO4) and concentrated. The oil was purified by flash chromatography (Biotage; 0%-50% EtOAc/hexane; 10 CV) to give (S)-(2,4-difluoro-6-(pent-4-en-2-yloxy)phenyl)methanol (0.1344 g, 0.589 mmol, 39.2% yield) as a colorless oil. 1H NMR (400 MHz, CDCl3) δ: 6.59-6.28 (m, 2H), 6.07-5.71 (m, 1H), 5.30-5.02 (m, 2H), 4.69 (d, J=5.6 Hz, 2H), 4.49 (sxt, J=6.0 Hz, 1H), 2.61-2.39 (m, 2H), 2.32 (t, J=6.8 Hz, 1H), 1.40 (d, J=6.1 Hz, 3H).

Workup

  1. temperatureThe mixture was cooled to 0° C.
  2. customquenched dropwise with brine
  3. additionthen diluted with EtOAc and water
  4. washThe organic phase was washed with brine
  5. dry with materialdried (Na2SO4)
  6. concentrationconcentrated
  7. customThe oil was purified by flash chromatography (Biotage; 0%-50% EtOAc/hexane; 10 CV)

Sources & evidence

ORD record
ord-1d0cbb7ff57c4af4b70a882706c2eb59
Source dataset
uspto-grants-2016_03
Patent number
US09273067B2

Reaction notes

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