Iodoethane → (4S,7R)-1-ethyl-7,8,8-trimethyl-2-naphthalen-1-yl-1,2,4,5,6,7-hexahydro-4,7-methano-indazol-3-one
Reaction equation
[CH3:1][C@@:2]12[C:22]([CH3:24])([CH3:23])[C@@H:5]([C:6]3[C:7](=[O:21])[N:8]([C:11]4[C:20]5[C:15](=[CH:16][CH:17]=[CH:18][CH:19]=5)[CH:14]=[CH:13][CH:12]=4)[NH:9][C:10]=31)[CH2:4][CH2:3]2.I[CH2:26][CH3:27]>CN(C)C=O>[CH2:26]([N:9]1[C:10]2[C@@:2]3([CH3:1])[C:22]([CH3:24])([CH3:23])[C@H:5]([CH2:4][CH2:3]3)[C:6]=2[C:7](=[O:21])[N:8]1[C:11]1[C:20]2[C:15](=[CH:16][CH:17]=[CH:18][CH:19]=2)[CH:14]=[CH:13][CH:12]=1)[CH3:27]Participants
Reactant 2
Product 1
Reagents, catalysts & solvents 1
Conditions
- Temperature
- 100 °C
Procedure
A mixture of (4S,7R)-7,8,8-trimethyl-2-naphthalen-1-yl-1,2,4,5,6,7-hexahydro-4,7-methano-indazol-3-one (Intermediate 46; 150 mg, 0.47 mmol) and iodoethane (151 μL, 1.88 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 12 g column, eluting with 90-100% ethyl acetate/hexanes to give (4S,7R)-1-ethyl-7,8,8-trimethyl-2-naphthalen-1-yl-1,2,4,5,6,7-hexahydro-4,7-methano-indazol-3-one (72 mg, 44%) as a light yellow foam. ES(+)-MS (M+H) 347.
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-9a76026794604c9cb8a68d19a8c09583
- Source dataset
- uspto-grants-2009_11
- Patent number
- US07622492B2
Reaction notes
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