Aluminium lithium hydride → (4-(4-Chloro-2-fluorophenyl)-6-methylpyridin-3-yl)methanol

HRID 870976Notes

Reaction equation

HRID 870976 reaction equation
[Cl:1][C:2]1[CH:7]=[CH:6][C:5]([C:8]2[C:13]([C:14](OC)=[O:15])=[CH:12][N:11]=[C:10]([CH3:18])[CH:9]=2)=[C:4]([F:19])[CH:3]=1.[H-].[H-].[H-].[H-].[Li+].[Al+3]>O1CCCC1.[NH4+].[Cl-]>[Cl:1][C:2]1[CH:7]=[CH:6][C:5]([C:8]2[CH:9]=[C:10]([CH3:18])[N:11]=[CH:12][C:13]=2[CH2:14][OH:15])=[C:4]([F:19])[CH:3]=1

Participants

5

Reactant 2

HCID 21226445Aluminium lithium hydrideHCID 86695958Methyl 4-(4-chloro-2-fluorophenyl)-6-methylnicotinate

Product 1

HCID 86695959(4-(4-Chloro-2-fluorophenyl)-6-methylpyridin-3-yl)methanolYield 87%

Reagents, catalysts & solvents 2

HCID 8028TetrahydrofuranSolventHCID 25517Ammonium ChlorideSolvent

Procedure

To a solution of methyl 4-(4-chloro-2-fluorophenyl)-6-methylnicotinate (0.32 g, 1.144 mmol) in tetrahydrofuran (10 mL) at −10° C., LAH (1.716 mL, 1.716 mmol) was added portionwise. The reaction mixture was stirred for 2 h at RT then diluted with saturated aqueous NH4Cl (50 mL). The mixture was extracted with ethyl acetate (80 mL). The organic layer was separated, dried over Na2SO4 and concentrated to afford (4-(4-chloro-2-fluorophenyl)-6-methylpyridin-3-yl) methanol (0.25 g, 0.993 mmol, 87% yield) as off-white solid. LCMS (ESI) m/e 252.0 [(M+H)+, calcd for C13H12ClFNO 252.0]; LC/MS retention time (Method H): tR=1.60 min; 1H NMR (400 MHz, CDCl3) δ 7.69 (s, 1H), 7.52 (s, 1H), 7.23 (s, 2H), 7.04-7.17 (m, 1H), 4.57 (d, J=11.60 Hz, 2H), 2.60 (s, 3H).

Workup

  1. extractionThe mixture was extracted with ethyl acetate (80 mL)
  2. customThe organic layer was separated
  3. dry with materialdried over Na2SO4
  4. concentrationconcentrated

Sources & evidence

ORD record
ord-a5e2143869294d0088c08656a6bc3f38
Source dataset
uspto-grants-2015_03
Patent number
US08969564B2

Reaction notes

Loading…