Potassium Carbonate → (R)-3-(4-Fluorophenoxy)butanoic acid

HRID 1693688Notes

Reaction equation

HRID 1693688 reaction equation
[F:1][C:2]1[CH:3]=[C:4]2[C:9](=[CH:10][CH:11]=1)[O:8][C@H:7]([CH3:12])[CH2:6][C:5]2=[O:13].Cl.NO.C([O-])([O-])=[O:18].[K+].[K+]>O>[F:1][C:2]1[CH:11]=[CH:10][C:9]([O:8][C@H:7]([CH3:12])[CH2:6][C:5]([OH:13])=[O:18])=[CH:4][CH:3]=1

Participants

5

Reactant 3

HCID 11430Potassium CarbonateHCID 443297Hydroxyamine hydrochlorideHCID 7154394HCID 7154394, compound

Product 1

HCID 57626400(R)-3-(4-Fluorophenoxy)butanoic acidYield 184.5%

Reagents, catalysts & solvents 1

HCID 962WaterSolvent

Procedure

6-fluoro-2,3-dihydro-2-methylchromen-4-oxime (13). To a suspension of the ketone 12 (2.79 g, 15.5 mmol) was added a solution of hydroxylamine hydrochloride (2.09 g, 30 mmol) and K2CO3 (1.2 g, 8.75 mmol) in 18 mL of H2O. The reaction mixture was refluxed for four hours. After cooling to room temperature, the solution was removed under vacuum, and the residual solid was triturated with ice water. The crude product was recrystallized from EtOH to give 3.2 g (84%) of the white solid oxime 13, m.p. 102-105° C., 1H NMR (CDCl3) δ 7.58 (br s, 1H), 7.48 (dd, J=3.0, 9.5 Hz, 1H), 6.97 (ddd, J=3.0, 9.0, 8.0 Hz, 1H), 6.85 (dd, J=4.5, 9.0 Hz, 1H), 4.21-4.15 (m, 1H), 3.28 (dd, J=3.0, 17.0 Hz, 1H), 2.37 (dd, J=12.0, 17.0 Hz, 1H), 1.47 (d, J=6.5 Hz, 3H). EI-MS (m/z) 195 (M+). The reaction is shown as follows:

Workup

  1. temperatureThe reaction mixture was refluxed for four hours
  2. customthe solution was removed under vacuum
  3. customthe residual solid was triturated with ice water
  4. customThe crude product was recrystallized from EtOH

Sources & evidence

ORD record
ord-6934df6784874f4da0216043c82093d2
Source dataset
uspto-grants-2012_04
Patent number
US08158667B2

Reaction notes

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