Allyl iodide → (4s,7r)-1-Allyl-2-(2,4-difluoro-phenyl)-7,8,8-trimethyl-1,2,4,5,6,7-hexahydro-4,7-methano-indazol-3-one
Reaction equation
[F:1][C:2]1[CH:7]=[C:6]([F:8])[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.[CH2:23](I)[CH:24]=[CH2:25]>CN(C)C=O>[CH2:25]([N:10]1[C:11]2[C@@:12]3([CH3:22])[C:19]([CH3:21])([CH3:20])[C@H:15]([CH2:14][CH2:13]3)[C:16]=2[C:17](=[O:18])[N:9]1[C:3]1[CH:4]=[CH:5][C:6]([F:8])=[CH:7][C:2]=1[F:1])[CH:24]=[CH2:23]Participants
Reactant 2
Product 1
Reagents, catalysts & solvents 1
Conditions
- Temperature
- 100 °C
Procedure
A mixture of (4S,7R)-2-(2,4-difluoro-phenyl)-7,8,8-trimethyl-1,2,4,5,6,7-hexahydro-4,7-methano-indazol-3-one (Intermediate 14; 420 mg, 1.38 mmol) and allyl iodide (600 μL, 5.5 mmol) in dimethylformamide (5 mL) was heated in an oil-bath at 100° C. for 8 h. The solvent was evaporated and the residue was partitioned between dichloromethane and water. The aqueous layer was extracted with dichloromethane (2×100 mL) and the combined organic layers were washed with water (5×100 mL) and aqueous sodium thiosulfate (100 mL). The solvent was evaporated and the residue was purified using an ISCO 40 g column, eluting with 90-100% ethyl acetate/hexanes to give (4S,7R)-1-allyl-2-(2,4-difluoro-phenyl)-7,8,8-trimethyl-1,2,4,5,6,7-hexahydro-4,7-methano-indazol-3-one (313 mg, 66%) as a white solid. APCI(+)-MS (M+H) 345.
Workup
- customThe solvent was evaporated
- customthe residue was partitioned between dichloromethane and water
- extractionThe aqueous layer was extracted with dichloromethane (2×100 mL)
- washthe combined organic layers were washed with water (5×100 mL) and aqueous sodium thiosulfate (100 mL)
- customThe solvent was evaporated
- customthe residue was purified
- washeluting with 90-100% ethyl acetate/hexanes
Sources & evidence
- ORD record
- ord-f946b3e06a82458780038483fa17d818
- Source dataset
- uspto-grants-2009_11
- Patent number
- US07622492B2
Reaction notes
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