Sodium borohydride → 3-Chloro-5-(4-(hydroxy(phenyl)methyl)phenyl)isonicotinonitrile

HRID 81031Notes

Reaction equation

HRID 81031 reaction equation
[BH4-].[Na+].[C:3]([C:11]1[CH:16]=[CH:15][C:14]([C:17]2[CH:24]=[N:23][CH:22]=[C:21]([Cl:25])[C:18]=2[C:19]#[N:20])=[CH:13][CH:12]=1)(=[O:10])[C:4]1[CH:9]=[CH:8][CH:7]=[CH:6][CH:5]=1>ClCCl.CO>[Cl:25][C:21]1[CH:22]=[N:23][CH:24]=[C:17]([C:14]2[CH:13]=[CH:12][C:11]([CH:3]([OH:10])[C:4]3[CH:5]=[CH:6][CH:7]=[CH:8][CH:9]=3)=[CH:16][CH:15]=2)[C:18]=1[C:19]#[N:20]

Participants

5

Reactant 2

HCID 4311764Sodium borohydrideHCID 669274923-(4-Benzoylphenyl)-5-chloroisonicotinonitrile

Product 1

HCID 669270213-Chloro-5-(4-(hydroxy(phenyl)methyl)phenyl)isonicotinonitrileYield 85.9%

Reagents, catalysts & solvents 2

HCID 887MethanolSolventHCID 6344DichloromethaneSolvent

Procedure

Granular sodium borohydride (225 mg, 5.94 mmol) was added to a solution of 3-(4-benzoylphenyl)-5-chloroisonicotinonitrile (473 mg, 1.187 mmol, 80% pure) in dichloromethane (10 mL) and methanol (10 mL). After 30 min at room temperature, the mixture was quenched with saturated ammonium chloride (30 mL). The organic solvents were evaporated in vacuo. The aqueous residue was extracted with ethyl acetate (2×40 mL). The combined extracts were washed with brine (5 mL), dried (MgSO4) and concentrated. Silica gel chromatography, loading with dichloromethane and eluting with 20-60% ethyl acetate in hexanes, gave 3-chloro-5-(4-(hydroxy(phenyl)methyl)phenyl)isonicotinonitrile as white solid (327 mg, 69% yield), which was approximately 80% pure. MS (ES+) m/z: 303 (M−water+H); LC retention time: 3.798 min (analytical HPLC Method A).

Workup

  1. customthe mixture was quenched with saturated ammonium chloride (30 mL)
  2. customThe organic solvents were evaporated in vacuo
  3. extractionThe aqueous residue was extracted with ethyl acetate (2×40 mL)
  4. washThe combined extracts were washed with brine (5 mL)
  5. dry with materialdried (MgSO4)
  6. concentrationconcentrated
  7. washeluting with 20-60% ethyl acetate in hexanes

Sources & evidence

ORD record
ord-d3446b37085b47529fd62d53781c644c
Source dataset
uspto-grants-2014_09
Patent number
US08846673B2

Reaction notes

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