Dichloromethane → HCID 57941382, compound

HRID 1438026Notes

Reaction equation

HRID 1438026 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.Cl[CH2:24][CH2:25][C:26]([C:28]1[CH:33]=[CH:32][CH:31]=[CH:30][CH:29]=1)=[O:27].ClCCl>[I-].C([N+](CCCC)(CCCC)CCCC)CCC.CN(C)C=O>[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][CH2:25][C:26](=[O:27])[C:28]1[CH:33]=[CH:32][CH:31]=[CH:30][CH:29]=1

Participants

6

Reactant 3

HCID 6344DichloromethaneHCID 702953-ChloropropiophenoneHCID 57941339(4s,7r)-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 57941382HCID 57941382, compoundYield 61.5%

Reagents, catalysts & solvents 2

HCID 67553Tetrabutylammonium IodideCatalystHCID 6228DimethylformamideSolvent

Conditions

Temperature
100 °C

Procedure

A mixture of (4S,7R)-2-(2,4-difluoro-phenyl)-7,8,8-trimethyl-1,2,4,5,6,7-hexahydro-4,7-methano-indazol-3-one (Intermediate 14; 330 mg, 1.08 mmol), tetrabutylammonium iodide (400 mg, 1.08 mmol) and 3-chloropropiophenone (Acros; 820 mg, 4.86 mmol) in dimethylformamide (6 mL) was heated at 100° C. for 3.5 h. The reaction mixture was cooled to room temperature. Dichloromethane (100 mL) was added and the solution was washed with water (4×25 mL), aqueous sodium thiosulfate (25 mL), and brine (25 mL). The solution was dried (magnesium sulfate), filtered, evaporated, and purified using an ISCO 40 g column, eluting with 50-100% ethyl acetate/hexane. The resulting material was dried under high vacuum at 70° C. for 3 h to give (4S,7R)-2-(2,4-difluoro-phenyl)-7,8,8-trimethyl-1-(3-oxo-3-phenyl-propyl)-1,2,4,5,6,7-hexahydro-4,7-methano-indazol-3-one (290 mg, 61%) as a tan solid. APCI(+)-MS (M+H) 437.

Workup

  1. temperatureThe reaction mixture was cooled to room temperature
  2. washthe solution was washed with water (4×25 mL), aqueous sodium thiosulfate (25 mL), and brine (25 mL)
  3. dry with materialThe solution was dried (magnesium sulfate)
  4. filtrationfiltered
  5. customevaporated
  6. custompurified
  7. washeluting with 50-100% ethyl acetate/hexane
  8. customThe resulting material was dried under high vacuum at 70° C. for 3 h

Sources & evidence

ORD record
ord-270408006acd4e5c88254f2f3cb25d20
Source dataset
uspto-grants-2009_11
Patent number
US07622492B2

Reaction notes

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