Hexane → 5-(4'-Acetamidomethyl-2'-methylbiphenyl-4-carbonyl)-1'-methyl-2,3,6,7-tetrahydrospiro[furo[2,3-f]indole-3,4'-piperidine]

HRID 1741101Notes

Reaction equation

[CH3:1][N:2]1[CH2:7][CH2:6][C:5]2([C:18]3[C:10](=[CH:11][C:12]4[CH2:13][CH2:14][NH:15][C:16]=4[CH:17]=3)[O:9][CH2:8]2)[CH2:4][CH2:3]1.C[Al](C)C.CCCCCC.[C:29]([NH:32][CH2:33][C:34]1[CH:39]=[CH:38][C:37]([C:40]2[CH:45]=[CH:44][C:43]([C:46](OC)=[O:47])=[CH:42][CH:41]=2)=[C:36]([CH3:50])[CH:35]=1)(=[O:31])[CH3:30]>C1(C)C=CC=CC=1.ClCCl>[C:29]([NH:32][CH2:33][C:34]1[CH:39]=[CH:38][C:37]([C:40]2[CH:45]=[CH:44][C:43]([C:46]([N:15]3[C:16]4[CH:17]=[C:18]5[C:5]6([CH2:8][O:9][C:10]5=[CH:11][C:12]=4[CH2:13][CH2:14]3)[CH2:4][CH2:3][N:2]([CH3:1])[CH2:7][CH2:6]6)=[O:47])=[CH:42][CH:41]=2)=[C:36]([CH3:50])[CH:35]=1)(=[O:31])[CH3:30]

Participants

Conditions

Temperature: 90 °C

Procedure

A stirred solution of 1'-methyl-2,3,6,7-tetrahydrospiro[furo[2,3-f]indole-3,4'-piperidine] (D8, 85 mg, 0.35 mmole) in toluene (10 ml) at room temperature under argon was treated with 2M trimethylaluminium in hexane (0.74 ml, 1.5 mmole). The mixture was stirred for 0.75 h, then treated with a solution of methyl 4'-acetamidomethyl-2'-methylbiphenyl-4-carboxylate (D21, 120 mg, 0.40 mmole) in toluene (5 ml) and heated at 90° C. for 2 h. The solution was allowed to cool, then poured carefully into a stirred slurry of silica gel (10 g) in dichloromethane (30 ml) and stirring continued until the effervescence had ceased. The silica gel slurry was then packed into a chromatography column and eluted with 0-10% MeOH/CH2Cl2 to afford the title compound (85 mg, 48%). This was converted to the oxalate salt, which crystallised form acetone.

Workup

temperatureto cool
stirringstirring
washeluted with 0-10% MeOH/CH2Cl2

Sources & evidence

ORD record: ord-76280d7f684840429e50ca142f277a4e
Source dataset: uspto-grants-1999_10
DOI: 10.6084/m9.figshare.5104873.v1
Patent number: US05972951

Reaction notes

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