m-Chloroperbenzoic acid → HCID 86713798, compound

HRID 521852Notes

Reaction equation

HRID 521852 reaction equation
[CH3:1][CH:2]1[CH:7]=[C:6]([CH3:8])[CH2:5][O:4][CH:3]1[C:9]1[N:13]([CH3:14])[N:12]=[CH:11][C:10]=1[N+:15]([O-:17])=[O:16].C1C=C(Cl)C=C(C(OO)=[O:26])C=1>C(Cl)Cl>[CH3:1][CH:2]1[CH:3]([C:9]2[N:13]([CH3:14])[N:12]=[CH:11][C:10]=2[N+:15]([O-:17])=[O:16])[O:4][CH2:5][C:6]2([CH3:8])[CH:7]1[O:26]2

Participants

4

Reactant 2

HCID 70297m-Chloroperbenzoic acid2×HCID 86713796HCID 86713796, compound

Product 1

HCID 86713798HCID 86713798, compound

Reagents, catalysts & solvents 1

HCID 6344DichloromethaneSolvent

Conditions

Temperature
0 °C

Procedure

To a solution of 5-(6-methoxy-3,5-dimethyl-3,6-dihydro-2H-pyran-2-yl)-1-methyl-4-nitro-pyrazole (100 mg, 0.38 mmol) in DCM (1 mL) cooled to −78° C. was added boron trifluoride diethyl etherate (0.14 mL, 1.13 mmol) and triethylsilane (0.36 mL), 2.68 mmol). After stirring at −78° C. for 1 hr, the reaction mixture was allowed to warm to room temperature and stirred for 18 hr. Saturated aqueous NaHCO3 (5 mL) and DCM (5 mL) were added and the organic layer was passed through a phase separation cartridge and concentrated under reduced pressure. Purification via silica gel column chromatography (0-60% EtOAc/isohexane) gave 5-(3,5-dimethyl-3,6-dihydro-2H-pyran-2-yl)-1-methyl-4-nitro-pyrazole as a yellow oil. The reaction was repeated to provide more material. To a solution of 5-(3,5-dimethyl-3,6-dihydro-2H-pyran-2-yl)-1-methyl-4-nitro-pyrazole (305 mg, 1.29 mmol) in DCM (6.5 mL) cooled to 0° C. was added m-CPBA (70-75%, 382 mg, 1.54 mmol) and the mixture was stirred at 0° C. for 90 min. More m-CPBA (70-75%, 191 mg, 0.774 mmol) was added and the mixture was slowly warmed to room temperature over 6 hr. The mixture was filtered through Celite® washing with DCM (15 mL) and the filtrate washed with saturated aqueous NaHCO3 (2×10 mL). The organic layer was passed through a phase separation cartridge and concentrated under reduced pressure. Purification via silica gel column chromatography (0-60% EtOAc/isohexane) gave 5-(2,6-dimethyl-4,7-dioxabicyclo[4.1.0]heptan-3-yl)-1-methyl-4-nitro-pyrazole as a single diastereomer as an off-white solid (189 mg, 53% over two steps). 1H NMR (400 MHz, CDCl3) δ 8.08 (s, 1H), 5.32-5.28 (m, 1H), 4.15-4.08 (m, 1H), 4.06 (s, 3H), 3.78 (d, J=12.9 Hz, 1H), 3.30 (d, J=5.6 Hz, 1H), 2.71-2.61 (m, 1H), 1.38 (s, 3H), 0.92 (d, J=7.0 Hz, 3H).

Workup

  1. customto provide more material
  2. temperaturethe mixture was slowly warmed to room temperature over 6 hr
  3. filtrationThe mixture was filtered through Celite®
  4. washwashing with DCM (15 mL)
  5. washthe filtrate washed with saturated aqueous NaHCO3 (2×10 mL)
  6. customThe organic layer was passed through a phase separation cartridge
  7. concentrationconcentrated under reduced pressure
  8. customPurification via silica gel column chromatography (0-60% EtOAc/isohexane)

Sources & evidence

ORD record
ord-f0f03512aea047468d501595e7c56f4f
Source dataset
uspto-grants-2016_05
Patent number
US09328106B2

Reaction notes

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