Isoxazole, 4-(chloromethyl)-3,5-dimethyl- → HCID 57941432, compound

HRID 1437951Notes

Reaction equation

[CH3:1][N:2]1[C:10]2[C@@:9]3([CH3:14])[C:11]([CH3:13])([CH3:12])[C@H:6]([CH2:7][CH2:8]3)[C:5]=2[C:4](=[O:15])[NH:3]1.Cl[CH2:17][C:18]1[C:19]([CH3:24])=[N:20][O:21][C:22]=1[CH3:23]>CN(C)C=O>[CH3:24][C:19]1[C:18]([CH2:17][N:3]2[C:4](=[O:15])[C:5]3[C@@H:6]4[C:11]([CH3:12])([CH3:13])[C@@:9]([CH3:14])([CH2:8][CH2:7]4)[C:10]=3[N:2]2[CH3:1])=[C:22]([CH3:23])[O:21][N:20]=1

Participants

Conditions

Temperature: 100 °C

Procedure

A mixture of (4S,7R)-1,7,8,8-tetramethyl-1,2,4,5,6,7-hexahydro-4,7-methano-indazol-3-one (Intermediate 19; 100 mg, 0.49 mmol) and 4-chloromethyl-3,5-dimethyl-isoxazole (60 μL, 0.48 mmol) in N,N-dimethylformamide (5 mL) was heated at 100° C. overnight. A further portion of and 4-chloromethyl-3,5-dimethyl-isoxazole (30 μL, 0.24 mmol) was added and the solution was heated at 100° C. for 2 h. The reaction mixture was evaporated and the residue was diluted with water and extracted with chloroform. The chloroform layer was washed with water, dried (magnesium sulfate), filtered, evaporated, and purified by flash chromatography, eluting with 3% methanol/dichloromethane to give (4S,7R)-2-(3,5-Dimethyl-isoxazol-4-ylmethyl)-1,7,8,8-tetramethyl-1,2,4,5,6,7-hexahydro-4,7-methano-indazol-3-one (62 mg, 41%) as an off-white solid. ES(+)-MS (M+H) 316.

Workup

temperaturethe solution was heated at 100° C. for 2 h
customThe reaction mixture was evaporated
additionthe residue was diluted with water
extractionextracted with chloroform
washThe chloroform layer was washed with water
dry with materialdried (magnesium sulfate)
filtrationfiltered
customevaporated
custompurified by flash chromatography
washeluting with 3% methanol/dichloromethane

Sources & evidence

ORD record: ord-66eff69d23814faea9fb1a6e4a92c66a
Source dataset: uspto-grants-2009_11
DOI: 10.6084/m9.figshare.5104873.v1
Patent number: US07622492B2

Reaction notes

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