Tetrahydrofuran → 5-[4'-Cyano-2'-methylbiphenyl-4-carbonyl]-1'-methyl-2,3,6,7-tetrahydrospiro[furo[2,3-f]indole-3,4'-piperidine]

Reaktionsgleichung

[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([N:21]([CH2:24][CH3:25])CC)C.[CH2:26]1[CH2:30][O:29][CH2:28][CH2:27]1>>[C:24]([C:25]1[CH:11]=[CH:10][C:18]([C:17]2[CH:28]=[CH:27][C:26]([C:30]([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:29])=[CH:12][CH:16]=2)=[C:5]([CH3:6])[CH:4]=1)#[N:21]

Komponenten

Edukt 3

HCID 8028Tetrahydrofuran2×

HCID 8471Triethylamine

HCID 106579521'-Methyl-6,7-dihydro-2H,5H-spiro[furo[2,3-f]indole-3,4'-piperidine]

Produkt 1

HCID 218337825-[4'-Cyano-2'-methylbiphenyl-4-carbonyl]-1'-methyl-2,3,6,7-tetrahydrospiro[furo[2,3-f]indole-3,4'-piperidine]Ausbeute 34 %

Versuchsvorschrift

A stirred suspension of 4'-cyano-2'-methylbiphenyl-4-carboxylic acid (D16) (0.3 g, 1.3 mmole) in dichloromethane (10 ml) at room temperature under argon was treated with oxalyl chloride (0.12 ml, 1.43 mmole), followed by DMF (1 drop). The mixture was stirred for 2 h, then concentrated in vacuo to leave the acid chloride as a pale yellow solid. This was dissolved in dry THF (8 ml) and added to a stirred solution of 1'-methyl-2,3,6,7-tetrahydrospiro[furo[2,3-f]indole-3,4'-piperidine] (D8) (0.3 g, 1.3 mmole) and triethylamine (0.35 ml, 2.6 mmole) in dry THF (10 ml) at 5° C. under argon. The reaction mixture was allowed to warm to room temperature and then concentrated in vacuo. The residue was taken up in 10% Na2CO3 solution (20 ml) and extracted with EtOAc (2×30 ml). The combined extract was dried (Na2SO4) concentrated in vacuo and the residue chromatographed on silica gel eluting with 1% methanol/dichloromethane to give the title compound (0.2 g, 34%) as a white solid.