Methyl iodide → HCID 57941467, compound

HRID 1437929Notes

Reaction equation

HRID 1437929 reaction equation
[CH3:1][C:2]1[C:7]([CH3:8])=[CH:6][CH:5]=[CH:4][C:3]=1[N:9]1[C:17](=[O:18])[C:16]2[C@@H:15]3[C:19]([CH3:21])([CH3:20])[C@@:12]([CH3:22])([CH2:13][CH2:14]3)[C:11]=2[NH:10]1.IC.[C:25](=O)(O)[O-].[Na+]>CN(C)C=O>[CH3:1][C:2]1[C:7]([CH3:8])=[CH:6][CH:5]=[CH:4][C:3]=1[N:9]1[C:17](=[O:18])[C:16]2[C@@H:15]3[C:19]([CH3:21])([CH3:20])[C@@:12]([CH3:22])([CH2:13][CH2:14]3)[C:11]=2[N:10]1[CH3:25]

Participants

5

Reactant 3

HCID 6328Methyl iodideHCID 516892Sodium BicarbonateHCID 57941378HCID 57941378, compound2×

Product 1

HCID 57941467HCID 57941467, compoundYield 49%

Reagents, catalysts & solvents 1

HCID 6228DimethylformamideSolvent

Conditions

Temperature
105 °C

Procedure

A mixture of (4S,7R)-2-(2,3-dimethyl-phenyl)-7,8,8-trimethyl-1,2,4,5,6,7-hexahydro-4,7-methano-indazol-3-one (Intermediate 16; 4.07 g, 13.8 mmol) and iodomethane (1.5 mL, 24.1 mmol) in N,N-dimethylformamide (60 mL) in a sealed tube was heated to 105° C. and stirred for 1.5 h. The reaction mixture was allowed to cool and saturated sodium bicarbonate solution (200 mL) was added. A solid precipitated. Water (100 mL) was added, and the mixture was extracted with ethyl acetate (300 mL). The organic layer was washed with brine (300 mL), concentrated and purified by chromatography, eluting with 60-100% ethyl acetate/dichloromethane. Fractions containing the product were combined, evaporated, and recrystallized from ethyl acetate/hexanes to give (4S,7R)-2-(2,3-dimethyl-phenyl)-1,7,8,8-tetramethyl-1,2,4,5,6,7-hexahydro-4,7-methano-indazol-3-one (2.12 g 49%) as a white solid. ES(+)-MS (M+H) 311.

Workup

  1. temperatureto cool
  2. customA solid precipitated
  3. additionWater (100 mL) was added
  4. extractionthe mixture was extracted with ethyl acetate (300 mL)
  5. washThe organic layer was washed with brine (300 mL)
  6. concentrationconcentrated
  7. custompurified by chromatography
  8. washeluting with 60-100% ethyl acetate/dichloromethane
  9. additionFractions containing the product
  10. customevaporated
  11. customrecrystallized from ethyl acetate/hexanes

Sources & evidence

ORD record
ord-b33e228887264b86ab56865443cfba32
Source dataset
uspto-grants-2009_11
Patent number
US07622492B2

Reaction notes

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