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

HRID 415890Notes

Reaction equation

HRID 415890 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 27%

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, 11 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 (500 mL). The resultant was chilled to 10° C., and sodium sulfate decahydrate (2 g) was added. After 1 hr, another 2 g of sodium sulfate decahydrate added. After 2 h, the gel was filtered through a bed of celite and washed with EtOAc (3×100 mL). The filtrate was then washed with aq. 1 M HCl (50 mL) 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 1 hr
  4. waitAfter 2 h
  5. filtrationthe gel was filtered through a bed of celite
  6. washwashed with EtOAc (3×100 mL)
  7. washThe filtrate was then washed with aq. 1 M HCl (50 mL) 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-5d219e6cff9f4beba55fa4ffcb09bcc0
Source dataset
uspto-grants-2012_01
Patent number
US08088794B2

Reaction notes

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