Acetone → 3-Fluoro-α,α-dimethyl-4-pyridinemethanol

HRID 2368670Notes

Reaction equation

HRID 2368670 reaction equation
[F:1][C:2]1[CH:3]=[N:4][CH:5]=[CH:6][CH:7]=1.[Li+].CC([N-]C(C)C)C.[CH3:16][C:17]([CH3:19])=[O:18]>C1COCC1>[F:1][C:2]1[CH:3]=[N:4][CH:5]=[CH:6][C:7]=1[C:17]([OH:18])([CH3:19])[CH3:16]

Participants

5

Reactant 3

HCID 180AcetoneHCID 677943-FluoropyridineHCID 2724682Lithium diisopropylamide

Product 1

HCID 131295773-Fluoro-α,α-dimethyl-4-pyridinemethanol

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent

Procedure

3-Fluoropyridine (11.0 g, 113.0 mmol) in 100 mL of THF was treated with LDA (1.5M, 100.0 mL, 150.0 mmol) at −78° C. for 50 min under argon. Acetone (28 mL) was added and the resulting reaction mixture was stirred at −78° C. to −40° C. for 50 min. The reaction was then quenched with aqueous NH4Cl and extracted with ether. The combined organic layers were washed with H2O and brine, then dried over Na2SO4 and concentrated under vacuum. Purification by MPLC (80 g column, 0 to 40% ethyl acetate in hexane as eluant) afforded the title compound. Spectroscopic data: 1H-NMR (300 MHz, CDCl3): δ ppm 1.65 (s, 6 H), 7.27 (dd, J=5.57 Hz, 1 H), 8.36-8.39 (m, 2 H).

Workup

  1. customthe resulting reaction mixture
  2. customThe reaction was then quenched with aqueous NH4Cl
  3. extractionextracted with ether
  4. washThe combined organic layers were washed with H2O and brine
  5. dry with materialdried over Na2SO4
  6. concentrationconcentrated under vacuum
  7. customPurification by MPLC (80 g column, 0 to 40% ethyl acetate in hexane as eluant)

Sources & evidence

ORD record
ord-0b1a3deffe2544b0bbea81136c189aaa
Source dataset
uspto-grants-2014_04
Patent number
US08703797B2

Reaction notes

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