Dichloromethane → HCID 57941317, compound

HRID 1438020Notes

Reaction equation

HRID 1438020 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.Br[CH2:24][C:25]1[CH:34]=[CH:33][C:28]([C:29]([O:31][CH3:32])=[O:30])=[CH:27][CH:26]=1.ClCCl>[I-].C([N+](CCCC)(CCCC)CCCC)CCC.CN(C)C=O>[CH3:32][O:31][C:29](=[O:30])[C:28]1[CH:33]=[CH:34][C:25]([CH2:24][N:10]2[C:11]3[C@:12]4([CH3:22])[C:19]([CH3:21])([CH3:20])[C@@H:15]([CH2:14][CH2:13]4)[C:16]=3[C:17](=[O:18])[N:9]2[C:3]2[CH:4]=[CH:5][C:6]([F:8])=[CH:7][C:2]=2[F:1])=[CH:26][CH:27]=1

Participants

6

Reactant 3

HCID 6344DichloromethaneHCID 256687Methyl 4-(bromomethyl)benzoateHCID 57941350(4r,7s)-2-(2,4-Difluoro-phenyl)-7,8,8-trimethyl-1,2,4,5,6,7-hexahydro-4,7-methano-indazol-3-one2×

Product 1

HCID 57941317HCID 57941317, compoundYield 49%

Reagents, catalysts & solvents 2

HCID 67553Tetrabutylammonium IodideCatalystHCID 6228DimethylformamideSolvent

Procedure

A solution of (4R,7S)-2-(2,4-difluoro-phenyl)-7,8,8-trimethyl-1,2,4,5,6,7-hexahydro-4,7-methano-indazol-3-one (Intermediate 42; 300 mg, 0.99 mmol), tetrabutylammonium iodide (270 mg, 0.7 mmol) and methyl 4-(bromomethyl)benzoate (1.00 g, 4.37 mmol) in dimethylformamide (10 mL) was heated at 100° C. for 3 h. The reaction mixture was allowed to cool. Dichloromethane (100 mL) was added, and the solution was washed with (5×25 mL), aqueous sodium thiosulfate (25 mL), and brine (25 mL), dried (magnesium sulfate, filtered, and evaporated. The residue was purified using an ISCO 40 g column, eluting with 50-100% ethyl acetate/hexanes. Fractions containing the product were concentrated and then dried under high vacuum at 50° C. give 4-[(4R,7S)-2-(2,4-difluoro-phenyl)-7,8,8-trimethyl-3-oxo-2,3,4,5,6,7-hexahydro-4,7-methano-indazol-1-ylmethyl]-benzoic acid methyl ester (219 mg, 49%) as a pale yellow solid. ES(+)-MS (M+H) 453.

Workup

  1. temperatureto cool
  2. washthe solution was washed with (5×25 mL), aqueous sodium thiosulfate (25 mL), and brine (25 mL)
  3. dry with materialdried (magnesium sulfate
  4. filtrationfiltered
  5. customevaporated
  6. customThe residue was purified
  7. washeluting with 50-100% ethyl acetate/hexanes
  8. additionFractions containing the product
  9. concentrationwere concentrated
  10. customdried under high vacuum at 50° C.

Sources & evidence

ORD record
ord-8826fc00d8b94b0b8288ea30a35c8cad
Source dataset
uspto-grants-2009_11
Patent number
US07622492B2

Reaction notes

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