Sodium Hydroxide → [5-(4-Fluoro-Phenyl)-2-Piperidin-4-yl-Oxazol-4-yl]Methanol

HRID 2288985Notes

Reaction equation

HRID 2288985 reaction equation
[F:1][C:2]1[CH:7]=[CH:6][C:5]([C:8]2[O:12][C:11]([CH:13]3[CH2:18][CH2:17][N:16](C(=O)C)[CH2:15][CH2:14]3)=[N:10][C:9]=2[CH2:22][OH:23])=[CH:4][CH:3]=1.[OH-].[Na+]>C(O)C.O>[F:1][C:2]1[CH:7]=[CH:6][C:5]([C:8]2[O:12][C:11]([CH:13]3[CH2:14][CH2:15][NH:16][CH2:17][CH2:18]3)=[N:10][C:9]=2[CH2:22][OH:23])=[CH:4][CH:3]=1

Participants

5

Reactant 2

HCID 14798Sodium HydroxideHCID 187004631-(4-[5-(4-Fluoro-phenyl)-4-hydroxymethyl-oxazol-2-yl]-piperidin-1-yl)-ethanone

Product 1

HCID 18700441[5-(4-Fluoro-Phenyl)-2-Piperidin-4-yl-Oxazol-4-yl]MethanolYield 73%

Reagents, catalysts & solvents 2

HCID 702EthanolSolventHCID 962WaterSolvent

Procedure

A solution of 1-{4-[5-(4-fluoro-phenyl)-4-hydroxymethyl-oxazol-2-yl]-piperidin-1-yl}-ethanone (1.0 g; 3.14 mmol) in 95% ethanol (10 ml) is treated with a solution of sodium hydroxide (2.5 g; 62.9 mmol) in water (5 ml) and the heterogeneous mixture heated at 75 C. for three hours. The ethanol is removed in a rotary evaporator and the residue is diluted with water (10 ml) and extracted with ethyl acetate (3×20 ml) and chloroform (3×20 ml). The organic phases are washed with saturated brine (10 ml), dried over sodium sulfate and concentrated to dryness. Purification by radial chromatography on silica gel using a methanol/dichloromethane gradient (5%-30%) containing 5% triethylamine afforded the product as an orange solid (0.63 g; 73%). HNMR (CD3OD): 7.34 (dd, 2H, J=8.7; 5.6 Hz), 6.80 (t, 2H, J=8.7 Hz), 4.29 (s, 2H), 2.82 (m, 2H), 2.66 (m, 1H), 2.41 (m, 2H), 1.76 (m, 2H), 1.49 (m, 2H).

Workup

  1. temperaturethe heterogeneous mixture heated at 75 C
  2. customThe ethanol is removed in a rotary evaporator
  3. additionthe residue is diluted with water (10 ml)
  4. extractionextracted with ethyl acetate (3×20 ml) and chloroform (3×20 ml)
  5. washThe organic phases are washed with saturated brine (10 ml)
  6. dry with materialdried over sodium sulfate
  7. concentrationconcentrated to dryness
  8. customPurification by radial chromatography on silica gel using a methanol/dichloromethane gradient (5%-30%)
  9. additioncontaining 5% triethylamine

Sources & evidence

ORD record
ord-f61e92d89cef42378e332b8e3213be19
Source dataset
uspto-grants-2000_07
Patent number
US06090825

Reaction notes

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