Dichloromethane → HCID 57941316, compound

HRID 1438091Notes

Reaction equation

HRID 1438091 reaction equation
[CH3:1][C@@:2]12[C:17]([CH3:19])([CH3:18])[C@@H:5]([C:6]3[C:7](=[O:16])[N:8]([CH2:11][C:12]([F:15])([F:14])[F:13])[NH:9][C:10]=31)[CH2:4][CH2:3]2.[CH2:20](Br)[C:21]1[CH:26]=[CH:25][CH:24]=[CH:23][CH:22]=1.ClCCl>[I-].C([N+](CCCC)(CCCC)CCCC)CCC.CN(C)C=O>[CH2:20]([N:9]1[C:10]2[C@@:2]3([CH3:1])[C:17]([CH3:19])([CH3:18])[C@H:5]([CH2:4][CH2:3]3)[C:6]=2[C:7](=[O:16])[N:8]1[CH2:11][C:12]([F:13])([F:14])[F:15])[C:21]1[CH:26]=[CH:25][CH:24]=[CH:23][CH:22]=1

Participants

6

Reactant 3

HCID 6344DichloromethaneHCID 7498Benzyl BromideHCID 57941325HCID 57941325, compound2×

Product 1

HCID 57941316HCID 57941316, compoundYield 70%

Reagents, catalysts & solvents 2

HCID 67553Tetrabutylammonium IodideCatalystHCID 6228DimethylformamideSolvent

Conditions

Temperature
100 °C

Procedure

A mixture of (4S,7R)-7,8,8-trimethyl-2-(2,2,2-trifluoro-ethyl)-1,2,4,5,6,7-hexahydro-4,7-methano-indazol-3-one (Intermediate 47; 150 mg, 0.55 mmol), tetrabutylammonium iodide (220 mg, 0.60 mmol) and benzyl bromide (580 μL, 4.9 mmol) in dimethylformamide (2 mL) was heated in a pressure tube in an oil-bath at 100° C. for 20 h. Dichloromethane (75 mL) was added and the solution was washed with water (5×25 mL) and aqueous sodium thiosulfate (25 mL), dried (magnesium sulfate), filtered, evaporated and purified using an ISCO 40 g column, eluting with 20-100% ethyl acetate/hexanes. Fractions homogeneous for the product were evaporated, co-evaporated with petroleum ether, triturated with petroleum ether, evaporated, and dried under high vacuum at 70° C. overnight to give (4S,7R)-1-benzyl-7,8,8-trimethyl-2-(2,2,2-trifluoro-ethyl)-1,2,4,5,6,7-hexahydro-4,7-methano-indazol-3-one (139 mg, 70%) as a white solid. ES(+)-MS (M+H) 365.

Workup

  1. washthe solution was washed with water (5×25 mL) and aqueous sodium thiosulfate (25 mL)
  2. dry with materialdried (magnesium sulfate)
  3. filtrationfiltered
  4. customevaporated
  5. custompurified
  6. washeluting with 20-100% ethyl acetate/hexanes
  7. customFractions homogeneous for the product were evaporated
  8. customtriturated with petroleum ether
  9. customevaporated
  10. customdried under high vacuum at 70° C. overnight

Sources & evidence

ORD record
ord-0248601aad4a4ffda57399d048f56d46
Source dataset
uspto-grants-2009_11
Patent number
US07622492B2

Reaction notes

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