Lithium borohydride → 5-Fluoro-4-(2-hydroxyethyl)-2-methoxybenzonitrile

HRID 1519540Notes

Reaction equation

HRID 1519540 reaction equation
C[O:2][C:3](=O)[CH2:4][C:5]1[CH:10]=[C:9]([O:11][CH3:12])[C:8]([C:13]#[N:14])=[CH:7][C:6]=1[F:15].[BH4-].[Li+]>O1CCCC1>[F:15][C:6]1[C:5]([CH2:4][CH2:3][OH:2])=[CH:10][C:9]([O:11][CH3:12])=[C:8]([CH:7]=1)[C:13]#[N:14]

Participants

4

Reactant 2

HCID 4148881Lithium borohydrideHCID 86694457Methyl (4-cyano-2-fluoro-5-methoxyphenyl)acetate

Product 1

HCID 666439605-Fluoro-4-(2-hydroxyethyl)-2-methoxybenzonitrile

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent

Procedure

To a solution of methyl(4-cyano-2-fluoro-5-methoxyphenyl)acetate (212 mg, 0.95 mmol) in tetrahydrofuran (4 mL) at 0° C. was added lithium borohydride (2.0 M solution in tetrahydrofuran, 0.62 mL). The mixture warmed slowly to room temperature and was quenched with saturated sodium bicarbonate and diluted with ethyl acetate. The layers were separated and the aqueous extracted with ethyl acetate (2×). The combined organics were washed with water and brine, then dried (Na2SO4), filtered and concentrated. The residue was purified by column chromatography (MPLC, 5-60% Ethyl Acetate:Hexanes) to provide 5-fluoro-4-(2-hydroxyethyl)-2-methoxybenzonitrile. 1H-NMR (500 MHz, CD3OD) δ ppm 7.22 (m, 1H), 6.92 (m, 1H), 3.93 (s, 3H), 3.88 (m, 2H), 2.95 (m, 2H), 2.29 (br s, 1H).

Workup

  1. customwas quenched with saturated sodium bicarbonate
  2. additiondiluted with ethyl acetate
  3. customThe layers were separated
  4. extractionthe aqueous extracted with ethyl acetate (2×)
  5. washThe combined organics were washed with water and brine
  6. dry with materialdried (Na2SO4)
  7. filtrationfiltered
  8. concentrationconcentrated
  9. customThe residue was purified by column chromatography (MPLC, 5-60% Ethyl Acetate:Hexanes)

Sources & evidence

ORD record
ord-3b7f364d004f496c97fb9c2b6a7d9acd
Source dataset
uspto-grants-2015_07
Patent number
US09073882B2

Reaction notes

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