Isobutylene oxide → Benzyl 1-(2-hydroxy-2-methylpropyl)-5-methyl-3-oxo-2-phenyl-2,3-dihydro-1H-pyrazole-4-carboxylate

HRID 2356358Notes

Reaction equation

HRID 2356358 reaction equation
[OH:1][C:2]1[N:6]([C:7]2[CH:12]=[CH:11][CH:10]=[CH:9][CH:8]=2)[N:5]=[C:4]([CH3:13])[C:3]=1[C:14]([O:16][CH2:17][C:18]1[CH:23]=[CH:22][CH:21]=[CH:20][CH:19]=1)=[O:15].C[Al](C)C.[O:28]1[C:30]([CH3:32])([CH3:31])[CH2:29]1.O.O.O.O.O.O.O.O.O.O.S([O-])([O-])(=O)=O.[Na+].[Na+]>ClC1C=CC=CC=1.C1COCC1>[OH:28][C:30]([CH3:32])([CH3:31])[CH2:29][N:5]1[C:4]([CH3:13])=[C:3]([C:14]([O:16][CH2:17][C:18]2[CH:23]=[CH:22][CH:21]=[CH:20][CH:19]=2)=[O:15])[C:2](=[O:1])[N:6]1[C:7]1[CH:8]=[CH:9][CH:10]=[CH:11][CH:12]=1

Participants

7

Reactant 4

HCID 11208Isobutylene oxideHCID 62649Sodium sulfate decahydrate2×HCID 16682925TrimethylaluminumHCID 178433862HCID 178433862, compound

Product 1

HCID 59383927Benzyl 1-(2-hydroxy-2-methylpropyl)-5-methyl-3-oxo-2-phenyl-2,3-dihydro-1H-pyrazole-4-carboxylateYield 291.8%

Reagents, catalysts & solvents 2

HCID 7964ChlorobenzeneSolventHCID 8028TetrahydrofuranSolvent

Conditions

Temperature
25 °C

Procedure

To a stirring suspension of benzyl 5-hydroxy-3-methyl-1-phenyl-1H-pyrazole-4-carboxylate (3380 mg, 1 mmol) in chlorobenzene (30 mL) at 10° C. under nitrogen was added trimethylaluminum (16 mL, 33 mmol, 2M in toluene). Internal temperature reached 27° C. At 25° C., 1,2-epoxy-2-methylpropane (1000 mg, 16 mmol) was added. The reaction mixture was stirred for 3 h at 25° C., and then diluted with THF (500mL). The resultant was chilled to 10° C., and sodium sulfate decahydrate (2g) was added. After 1hr, another 2 g of sodium sulfate decahydrate added. After 2 h, the gel was filtered through a bed of celite and washed with EtOAc (3×100mL). The filterate was then washed with aq. 1M HCl (50mL) and brine. The organic layer was dried over MgSO4. and concentrated. The residue was purified on 120 g silica chromatography (30>90% EtOAc/hex). To give the title compound (1.11 g, 27% yield) as an amorphous solid. MS (ESI pos. ion) m/z: 381 (MH+). Calc'd exact mass for C22H24N2O4 380.

Workup

  1. customreached 27° C
  2. temperatureThe resultant was chilled to 10° C.
  3. waitAfter 1hr
  4. waitAfter 2 h
  5. filtrationthe gel was filtered through a bed of celite
  6. washwashed with EtOAc (3×100mL)
  7. washThe filterate was then washed with aq. 1M HCl (50mL) and brine
  8. dry with materialThe organic layer was dried over MgSO4
  9. concentrationand concentrated
  10. customThe residue was purified on 120 g silica chromatography (30>90% EtOAc/hex)

Sources & evidence

ORD record
ord-bf0d9d0e2d784e57b8670dcacbf8dd7c
Source dataset
uspto-grants-2010_07
Patent number
US07759344B2

Reaction notes

Loading…