Dichloromethane → HCID 57941376, compound

HRID 1438092Notes

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.Br[CH2:21][CH2:22][C:23]1[CH:28]=[CH:27][CH:26]=[CH:25][CH:24]=1.ClCCl>[I-].C([N+](CCCC)(CCCC)CCCC)CCC.CN(C)C=O>[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:13])([F:14])[F:15])[N:9]([CH2:21][CH2:22][C:23]4[CH:28]=[CH:27][CH:26]=[CH:25][CH:24]=4)[C:10]=31)[CH2:4][CH2:3]2

Participants

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 (2-bromoethyl)benzene (660 μL, 4.8 mmol) in dimethylformamide (2 mL) was heated in a pressure tube in an oil-bath at 100° C. for 24 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 methanol, and dried under high vacuum at 90° C. for 3 h to give (4S,7R)-7,8,8-trimethyl-1-phenethyl-2-(2,2,2-trifluoro-ethyl)-1,2,4,5,6,7-hexahydro-4,7-methano-indazol-3-one (24 mg, 12%) as a yellow gum. ES(+)-MS (M+H) 379.

Workup

washthe solution was washed with water (5×25 mL) and aqueous sodium thiosulfate (25 mL)
dry with materialdried (magnesium sulfate)
filtrationfiltered
customevaporated
custompurified
washeluting with 20-100% ethyl acetate/hexanes
customFractions homogeneous for the product were evaporated
customdried under high vacuum at 90° C. for 3 h

Sources & evidence

ORD record: ord-ef86c534ca4b48d289eb90f2ffa3b285
Source dataset: uspto-grants-2009_11
DOI: 10.6084/m9.figshare.5104873.v1
Patent number: US07622492B2

Reaction notes

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