Bromomethylcyclopropane → HCID 57941385, compound

HRID 1437984Notes

Reaction equation

HRID 1437984 reaction equation
[Cl:1][C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][C:3]=1[N:8]1[C:16](=[O:17])[C:15]2[C@@H:14]3[C:18]([CH3:20])([CH3:19])[C@@:11]([CH3:21])([CH2:12][CH2:13]3)[C:10]=2[NH:9]1.Br[CH2:23][CH:24]1[CH2:26][CH2:25]1>[I-].C([N+](CCCC)(CCCC)CCCC)CCC.CN(C)C=O>[Cl:1][C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][C:3]=1[N:8]1[C:16](=[O:17])[C:15]2[C@@H:14]3[C:18]([CH3:20])([CH3:19])[C@@:11]([CH3:21])([CH2:12][CH2:13]3)[C:10]=2[N:9]1[CH2:23][CH:24]1[CH2:26][CH2:25]1

Participants

5

Reactant 2

HCID 81503BromomethylcyclopropaneHCID 57941362HCID 57941362, compound2×

Product 1

HCID 57941385HCID 57941385, compoundYield 33%

Reagents, catalysts & solvents 2

HCID 67553Tetrabutylammonium IodideCatalystHCID 6228DimethylformamideSolvent

Conditions

Temperature
100 °C

Procedure

A mixture of (4S,7R)-2-(2-chloro-phenyl)-7,8,8-trimethyl-1,2,4,5,6,7-hexahydro-4,7-methano-indazol-3-one (Intermediate 10; 154 mg, 0.51 mmol), tetrabutylammonium iodide (752 mg, 2.0 mmol), and (bromomethyl)cyclopropane (Lancaster; 195 μL, 2.0 mmol) in dimethylformamide (4.3 mL) was heated in an oil-bath at 100° C. for 16 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 120 g column, eluting with 65-100% ethyl acetate/hexanes to give (4S,7R)-2-(2-chloro-phenyl)-1-cyclopropylmethyl-7,8,8-trimethyl-1,2,4,5,6,7-hexahydro-4,7-methano-indazol-3-one (60 mg, 33%) as a yellow gum. ES(+)-MS (M+H) 357.

Workup

  1. customThe solvent was evaporated
  2. customthe residue was partitioned between dichloromethane and water
  3. extractionThe aqueous layer was extracted with dichloromethane (2×100 mL)
  4. washthe combined organic layers were washed with water (5×100 mL) and aqueous sodium thiosulfate (100 mL)
  5. customThe solvent was evaporated
  6. customthe residue was purified
  7. washeluting with 65-100% ethyl acetate/hexanes

Sources & evidence

ORD record
ord-53c65cd850f14319b37a9ef098286a59
Source dataset
uspto-grants-2009_11
Patent number
US07622492B2

Reaction notes

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