Sodium borohydride → 1-(3-Fluoropyridin-2-yl)-3-hydroxycyclobutane-1-carbonitrile

HRID 869211Notes

Reaction equation

HRID 869211 reaction equation
[F:1][C:2]1[C:3]([C:8]2([C:13]#[N:14])[CH2:11][C:10](=[O:12])[CH2:9]2)=[N:4][CH:5]=[CH:6][CH:7]=1.[BH4-].[Na+]>C(Cl)Cl.CO>[F:1][C:2]1[C:3]([C:8]2([C:13]#[N:14])[CH2:11][CH:10]([OH:12])[CH2:9]2)=[N:4][CH:5]=[CH:6][CH:7]=1

Participants

5

Reactant 2

HCID 4311764Sodium borohydrideHCID 674531411-(3-Fluoropyridin-2-yl)-3-oxocyclobutane-1-carbonitrile

Product 1

HCID 674530321-(3-Fluoropyridin-2-yl)-3-hydroxycyclobutane-1-carbonitrileYield 79.2%

Reagents, catalysts & solvents 2

HCID 887MethanolSolventHCID 6344DichloromethaneSolvent

Conditions

Temperature
-78 °C

Procedure

To a solution of 1-(3-fluoropyridin-2-yl)-3-oxocyclobutanecarbonitrile (231 g, 1.22 mol) in a mixture of DCM (2 L) and MeOH (200 mL) was added NaBH4 portion-wise at −78° C. The reaction mixture was stirred 1 h at −78° C. and then quenched with a mixture of methanol and water (1/1). The organic layer was washed with water (500 mL×3), dried over Na2SO4, and concentrated. The residue was purified on silica gel (50% EtOAc in Hexanes) to provide the title compound as an amber oil (185.8 g, 77.5%), LRMS (M+H+) m/z 193.2.

Workup

  1. customquenched with a mixture of methanol and water (1/1)
  2. washThe organic layer was washed with water (500 mL×3)
  3. dry with materialdried over Na2SO4
  4. concentrationconcentrated
  5. customThe residue was purified on silica gel (50% EtOAc in Hexanes)

Sources & evidence

ORD record
ord-a8372ee204c04cf58fae988cb19709c1
Source dataset
uspto-grants-2015_03
Patent number
US08969346B2

Reaction notes

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