Potassium Fluoride → 2-[5-(Fluoromethyl)isoxazol-3-yl]but-3-yn-2-ol

HRID 1398542Notes

Reaction equation

HRID 1398542 reaction equation
CC1C=CC(S(O[CH2:12][C:13]2[O:17][N:16]=[C:15]([C:18]([OH:22])([C:20]#[CH:21])[CH3:19])[CH:14]=2)(=O)=O)=CC=1.[F-:23].[K+]>C(#N)C>[F:23][CH2:12][C:13]1[O:17][N:16]=[C:15]([C:18]([OH:22])([C:20]#[CH:21])[CH3:19])[CH:14]=1

Participants

4

Reactant 2

HCID 522689Potassium FluorideHCID 86669584[3-(2-Hydroxybut-3-yn-2-yl)isoxazol-5-yl]methyl 4-methylbenzenesulfonate

Product 1

HCID 866695852-[5-(Fluoromethyl)isoxazol-3-yl]but-3-yn-2-ol

Reagents, catalysts & solvents 1

HCID 6342AcetonitrileSolvent

Procedure

To a solution of [3-(2-hydroxybut-3-yn-2-yl)isoxazol-5-yl]methyl 4-methylbenzenesulfonate (259 mg, 0.81 mmol) in dry acetonitrile (10 mL) was introduced potassium fluoride (94 mg, 1.61 mmol) and Kryptopfix® 222 (606 mg, 1.61 mmol). After 5 hr rapid stirring at RT, the reaction mixture was concentrated in vacuo and the residue partitioned between EtOAc (40 mL) and water (2×40 mL). The organic extract was washed with brine (30 mL), dried (Na2SO4), filtered and the filtrate adsorbed onto silica gel in vacuo. Purification by silica gel flash column chromatography (heptane/EtOAc gradient of increasing polarity) furnished the title compound as a colorless oil: 1H NMR (500 MHz, CDCl3) delta 1.91 (3H, s), 2.69 (1H, s), 2.86 (1H, s), 5.42 (1H, d, J=47.3 Hz), 6.55 (1H, d, J=2.8 Hz); 19F NMR-decoupled (235 MHz, CDCl3) delta −218.8 (s); LC-MS: m/z=+169.9 (M+H)+.

Workup

  1. concentrationthe reaction mixture was concentrated in vacuo
  2. customthe residue partitioned between EtOAc (40 mL) and water (2×40 mL)
  3. extractionThe organic extract
  4. washwas washed with brine (30 mL)
  5. dry with materialdried (Na2SO4)
  6. filtrationfiltered
  7. customPurification
  8. temperatureby silica gel flash column chromatography (heptane/EtOAc gradient of increasing polarity)

Sources & evidence

ORD record
ord-8fe513d413534537ac579f19bc6f2e5d
Source dataset
uspto-grants-2014_12
Patent number
US08901313B2

Reaction notes

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