Aluminium lithium hydride → (S)-(4,5-difluoro-2-(pent-4-en-2-yloxy)phenyl)methanol

HRID 921130Notes

Reaction equation

HRID 921130 reaction equation
[F:1][C:2]1[C:9]([F:10])=[CH:8][C:5]([CH:6]=[O:7])=[C:4]([O:11][C@H:12]([CH2:14][CH:15]=[CH2:16])[CH3:13])[CH:3]=1.[H-].[Al+3].[Li+].[H-].[H-].[H-]>C1COCC1>[F:1][C:2]1[C:9]([F:10])=[CH:8][C:5]([CH2:6][OH:7])=[C:4]([O:11][C@H:12]([CH2:14][CH:15]=[CH2:16])[CH3:13])[CH:3]=1

Participants

4

Reactant 2

HCID 21226445Aluminium lithium hydrideHCID 118307018(S)-4,5-difluoro-2-(pent-4-en-2-yloxy)benzaldehyde

Product 1

HCID 118307066(S)-(4,5-difluoro-2-(pent-4-en-2-yloxy)phenyl)methanolYield 83.4%

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent

Procedure

To a solution of (S)-4,5-difluoro-2-(pent-4-en-2-yloxy)benzaldehyde (0.1295 g, 0.572 mmol) in THF (2 ml) at 0° C. was added dropwise lithium aluminum hydride (0.343 ml, 0.687 mmol) over 30 min. The mixture was stirred at rt for 2 h then cooled to 0° C. and quenched by the dropwise addition of brine. The mixture was partitioned between EtOAc and water. The organic phase was washed with brine, dried (Na2SO4), filtered and concentrated to give (S)-(4,5-difluoro-2-(pent-4-en-2-yloxy)phenyl)methanol (0.1088 g, 0.477 mmol, 83% yield) as a yellow oil. 1H NMR (400 MHz, CDCl3) δ 7.15 (dd, J=10.4, 9.2 Hz, 1H), 6.72 (dd, J=12.0, 6.6 Hz, 1H), 5.99-5.70 (m, 1H), 5.24-5.07 (m, 2H), 4.75-4.49 (m, 2H), 4.41 (sxt, J=6.0 Hz, 1H), 2.60-2.35 (m, 2H), 2.26 (t, J=6.5 Hz, 1H), 1.36 (d, J=6.1 Hz, 3H).

Workup

  1. temperaturethen cooled to 0° C.
  2. customquenched by the dropwise addition of brine
  3. customThe mixture was partitioned between EtOAc and water
  4. washThe organic phase was washed with brine
  5. dry with materialdried (Na2SO4)
  6. filtrationfiltered
  7. concentrationconcentrated

Sources & evidence

ORD record
ord-372fcb597c6347aaaea3d7cba549b946
Source dataset
uspto-grants-2016_03
Patent number
US09273067B2

Reaction notes

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