3-Oxetanone → HCID 71272554, compound

HRID 475079Notes

Reaction equation

HRID 475079 reaction equation
[CH3:1][C:2]1[N:3]([C:8]2[CH:12]=[CH:11][N:10]([CH2:13][O:14][CH2:15][CH2:16][Si:17]([CH3:20])([CH3:19])[CH3:18])[N:9]=2)[C:4]([CH3:7])=[CH:5][CH:6]=1.C([Li])CCC.[O:26]1[CH2:29][C:28](=[O:30])[CH2:27]1>C1COCC1>[CH3:7][C:4]1[N:3]([C:8]2[CH:12]=[C:11]([C:28]3([OH:30])[CH2:29][O:26][CH2:27]3)[N:10]([CH2:13][O:14][CH2:15][CH2:16][Si:17]([CH3:18])([CH3:20])[CH3:19])[N:9]=2)[C:2]([CH3:1])=[CH:6][CH:5]=1

Participants

5

Reactant 3

HCID 150242543-OxetanoneHCID 71272748HCID 71272748, compoundHCID 178418339Butyllithium

Product 1

HCID 71272554HCID 71272554, compoundYield 86.3%

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent2×

Conditions

Temperature
-78 °C

Procedure

Into a 5 L 4-necked round-bottom flask under nitrogen was placed 3-(2,5-dimethyl-1H-pyrrol-1-yl)-1-[[2-(trimethylsilyl)ethoxy]methyl]-1H-pyrazole (132.0 g, 452.89 mmol, 1.00 equiv.) in THF (2 L), followed by the addition of butyl lithium (208 mL, 2.4 M, 1.10 equiv) dropwise with stirring at −78° C. over 15 min. The resulting solution was stirred at −50° C. for 40 min. To this was added a solution of oxetan-3-one (40.0 g, 555.07 mmol, 1.20 equiv) in THF (500 mL), dropwise with stirring at −78° C. over 30 min. The resulting solution was stirred at −78° C. for 30 min then quenched by the addition of 2 L of satd. aq. NH4Cl. The mixture was concentrated in vacuo and extracted with 3×1 L of EtOAc. The combined organic layers were washed with 2×1 L of water and 1×500 mL of brine, dried (Na2SO4) and concentrated in vacuo. The residue was purified by SiO2 chromatography eluting with EtOAc/petroleum ether (1:20-1:5) to afford 3-[3-(2,5-dimethyl-1H-pyrrol-1-yl)-1-[[2-(trimethylsilyl)ethoxy]methyl]-1H-pyrazol-5-yl]oxetan-3-ol (142.0 g, 82% yield) as a light yellow oil.

Workup

  1. customInto a 5 L 4-necked round-bottom flask under nitrogen was placed
  2. stirringThe resulting solution was stirred at −50° C. for 40 min
  3. stirringdropwise with stirring at −78° C. over 30 min
  4. stirringThe resulting solution was stirred at −78° C. for 30 min
  5. customthen quenched by the addition of 2 L of satd
  6. concentrationThe mixture was concentrated in vacuo
  7. extractionextracted with 3×1 L of EtOAc
  8. washThe combined organic layers were washed with 2×1 L of water and 1×500 mL of brine
  9. dry with materialdried (Na2SO4)
  10. concentrationconcentrated in vacuo
  11. customThe residue was purified by SiO2 chromatography
  12. washeluting with EtOAc/petroleum ether (1:20-1:5)

Sources & evidence

ORD record
ord-2a11275b3bda4e6d8f2cffb09b780d5d
Source dataset
uspto-grants-2014_01
Patent number
US08637537B2

Reaction notes

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