Iodoethane → (4r,7s)-2-(2,4-Difluoro-phenyl)-1-ethyl-7,8,8-trimethyl-1,2,4,5,6,7-hexahydro-4,7-methano-indazol-3-one

HRID 1437998Notes

Reaction equation

HRID 1437998 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.I[CH2:24][CH3:25]>CN1CCCC1.C(OCC)(=O)C>[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[N:10]1[CH2:24][CH3:25]

Participants

5

Reactant 2

HCID 6340IodoethaneHCID 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 57941329(4r,7s)-2-(2,4-Difluoro-phenyl)-1-ethyl-7,8,8-trimethyl-1,2,4,5,6,7-hexahydro-4,7-methano-indazol-3-oneYield 39.7%

Reagents, catalysts & solvents 2

HCID 84541-MethylpyrrolidineSolventHCID 8857Ethyl AcetateSolvent

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; 153 mg, 0.5 mmol) and iodoethane (0.21 mL, 2.6 mmol) in N-methylpyrrolidine (1 mL) was heated at 100° C. in a sealed tube for 17 h. The reaction mixture was purified by preparative HPLC to give a brown semi-solid which was dissolved in ethyl acetate. The solution was washed with 10% aqueous sodium thiosulfate (three times) and brine, dried (sodium sulfate), filtered, evaporated, and dried under high vacuum to give (4R,7S)-2-(2,4-difluoro-phenyl)-1-ethyl-7,8,8-trimethyl-1,2,4,5,6,7-hexahydro-4,7-methano-indazol-3-one (66 mg, 39%) as a pale yellow foam. ES(+)-MS (M+H) 333.

Workup

  1. customThe reaction mixture was purified by preparative HPLC
  2. customto give a brown semi-solid which
  3. washThe solution was washed with 10% aqueous sodium thiosulfate (three times) and brine
  4. dry with materialdried (sodium sulfate)
  5. filtrationfiltered
  6. customevaporated
  7. customdried under high vacuum

Sources & evidence

ORD record
ord-2083ba09b85b4b26ae530fbe7018a951
Source dataset
uspto-grants-2009_11
Patent number
US07622492B2

Reaction notes

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