Benzyl Bromide → (1R,7S)-3-benzyl-1,10,10-trimethyl-4-phenyl-3,4-diazatricyclo[5.2.1.02,6]dec-2(6)-en-5-one

HRID 1437912Notes

Reaction equation

[CH2:1](Br)[C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][CH:3]=1.[C:9]1([N:15]2[C:23](=[O:24])[C:22]3[C@@H:21]4[C:25]([CH3:27])([CH3:26])[C@@:18]([CH3:28])([CH2:19][CH2:20]4)[C:17]=3[NH:16]2)[CH:14]=[CH:13][CH:12]=[CH:11][CH:10]=1>[I-].C([N+](CCCC)(CCCC)CCCC)CCC.CN(C)C=O>[CH2:1]([N:16]1[C:17]2[C@@:18]3([CH3:28])[C:25]([CH3:27])([CH3:26])[C@H:21]([CH2:20][CH2:19]3)[C:22]=2[C:23](=[O:24])[N:15]1[C:9]1[CH:10]=[CH:11][CH:12]=[CH:13][CH:14]=1)[C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][CH:3]=1

Participants

Conditions

Temperature: 100 °C

Procedure

A mixture of benzyl bromide (3.87 mL, 31.9 mmol), (4S,7R)-2-phenyl-7,8,8-trimethyl-1,2,4,5,6,7-hexahydro-4,7-methano-indazol-3-one (Intermediate 6; 2.14 g, 8.0 mmol) and tetra-n-butylammonium iodide (2.06 g, 5.6 mmol) in N,N-dimethylformamide (50 mL) was heated in an oil-bath at 100° C. for 16 h. The solvent was evaporated and dichloromethane (100 mL) and water were added. The aqueous layer was extracted with dichloromethane (2×100 mL) and the combined organic layers were washed with water (5×100 mL). The solvent was evaporated and the residue purified on an Isco 120 g column, eluting with 33-100% ethyl acetate/hexanes to give (4S,7R)-1-benzyl-7,8,8-trimethyl-2-phenyl-1,2,4,5,6,7-hexahydro-4,7-methano-indazol-3-one (2.41 g, 84%) as an off-white/tan solid. ES(+)-MS (M+H) 359.

Workup

customThe solvent was evaporated
additiondichloromethane (100 mL) and water were added
extractionThe aqueous layer was extracted with dichloromethane (2×100 mL)
washthe combined organic layers were washed with water (5×100 mL)
customThe solvent was evaporated
customthe residue purified on an Isco 120 g column
washeluting with 33-100% ethyl acetate/hexanes

Sources & evidence

ORD record: ord-0c8bd28eaf5b42bb849cc6ade3d20670
Source dataset: uspto-grants-2009_11
DOI: 10.6084/m9.figshare.5104873.v1
Patent number: US07622492B2

Reaction notes

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