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

HRID 1474244Notes

Reaction equation

HRID 1474244 reaction equation
[C:1]([C:3]1[C:8]([O:9][CH3:10])=[CH:7][C:6]([CH2:11][C:12](OC)=[O:13])=[C:5]([F:16])[CH:4]=1)#[N:2].[BH4-].[Li+]>C1COCC1.[Cl-].[NH4+]>[F:16][C:5]1[C:6]([CH2:11][CH2:12][OH:13])=[CH:7][C:8]([O:9][CH3:10])=[C:3]([CH:4]=1)[C:1]#[N:2]

Participants

5

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 2

HCID 8028TetrahydrofuranSolventHCID 25517Ammonium ChlorideSolvent

Procedure

To a solution of methyl (4-Cyano-2-fluoro-5-methoxyphenyl)acetate (5.0 g, 22 mmol) in THF (50 mL) at 0° C. was added lithium borohydride (14.6 mL, 29.1 mmol). The reaction was stirred for 12 h, then was diluted with saturated ammonium chloride solution and extracted three times with ethyl acetate. The combined organic layers were washed with brine, dried (Na2SO4), filtered, and concentrated. Silica gel column chromatography (50->100% EtOAc:hex.) provided 5-fluoro-4-(2-hydroxyethyl)-2-methoxybenzonitrile. 1H NMR (500 MHz, CD3OD) δ 7.19 (d, J=5.3 Hz, 1H), 6.89 (d, J=5.4 Hz, 1H), 4.21 (br s, 1H), 3.88 (s, 3H), 3.82 (m, 2H), 2.92 (m, 2H); LC/MS: [(M+1)]+=196.2; tR=0.58 min.

Workup

  1. extractionextracted three times with ethyl acetate
  2. washThe combined organic layers were washed with brine
  3. dry with materialdried (Na2SO4)
  4. filtrationfiltered
  5. concentrationconcentrated

Sources & evidence

ORD record
ord-d13dacb687c74745b8e2e2764f927e2c
Source dataset
uspto-grants-2015_04
Patent number
US09018211B2

Reaction notes

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