Bromomethylcyclopropane → (4r,7s)-1-(Cyclopropyl)methyl-7,8,8-trimethyl-2-phenyl-1,2,4,5,6,7-hexahydro-4,7-methano-indazol-3-one

HRID 1437961Notes

Reaction equation

HRID 1437961 reaction equation
Br[CH2:2][CH:3]1[CH2:5][CH2:4]1.[C:6]1([N:12]2[C:20](=[O:21])[C:19]3[C@@H:18]4[C:22]([CH3:24])([CH3:23])[C@@:15]([CH3:25])([CH2:16][CH2:17]4)[C:14]=3[NH:13]2)[CH:11]=[CH:10][CH:9]=[CH:8][CH:7]=1>[I-].C([N+](CCCC)(CCCC)CCCC)CCC.CN(C)C=O>[CH:5]1([CH2:4][N:13]2[C:14]3[C@:15]4([CH3:25])[C:22]([CH3:24])([CH3:23])[C@@H:18]([CH2:17][CH2:16]4)[C:19]=3[C:20](=[O:21])[N:12]2[C:6]2[CH:7]=[CH:8][CH:9]=[CH:10][CH:11]=2)[CH2:3][CH2:2]1

Participants

5

Reactant 2

HCID 81503BromomethylcyclopropaneHCID 57941335(4s,7r)-2-Phenyl-7,8,8-trimethyl-1,2,4,5,6,7-hexahydro-4,7-methano-indazol-3-one2×

Product 1

HCID 69021385(4r,7s)-1-(Cyclopropyl)methyl-7,8,8-trimethyl-2-phenyl-1,2,4,5,6,7-hexahydro-4,7-methano-indazol-3-oneYield 49%

Reagents, catalysts & solvents 2

HCID 67553Tetrabutylammonium IodideCatalystHCID 6228DimethylformamideSolvent

Conditions

Temperature
100 °C

Procedure

A mixture of (bromomethyl)cyclopropane (263 μL, 2.75 mmol), (4R,7S)-2-phenyl-7,8,8-trimethyl-1,2,4,5,6,7-hexahydro-4,7-methano-indazol-3-one (Intermediate 6; 184 mg, 0.69 mmol) and tetra-n-butylammonium iodide (1.02 g, 2.75 mmol) in N,N-dimethylformamide (4.3 mL) was heated in an oil-bath at 100° C. for 16 h. The solvent was evaporated and dichloromethane (100 mL) and water were added. The aqueous layer was extracted with dichloromethane (2×100 mL) and the combined organic layers were washed with water (5×100 mL) and then with sodium thiosulfate solution (100 mL). The solvent was evaporated and the residue purified on an Isco 120 g column, eluting with 33-100% ethyl acetate/hexanes to give (4R,7S)-1-(cyclopropyl)methyl-7,8,8-trimethyl-2-phenyl-1,2,4,5,6,7-hexahydro-4,7-methano-indazol-3-one (108 mg, 49%) as an off-white/tan oil. APCI-MS (M+H) 323.

Workup

  1. customThe solvent was evaporated
  2. additiondichloromethane (100 mL) and water were added
  3. extractionThe aqueous layer was extracted with dichloromethane (2×100 mL)
  4. washthe combined organic layers were washed with water (5×100 mL)
  5. customThe solvent was evaporated
  6. customthe residue purified on an Isco 120 g column
  7. washeluting with 33-100% ethyl acetate/hexanes

Sources & evidence

ORD record
ord-ebf17bc14d2f4dd9aa1431e5f6dae66e
Source dataset
uspto-grants-2009_11
Patent number
US07622492B2

Reaction notes

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