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

HRID 1741098Notes

Reaction equation

HRID 1741098 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([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]

Participants

4

Reactant 3

HCID 8028Tetrahydrofuran2×HCID 8471TriethylamineHCID 106579521'-Methyl-6,7-dihydro-2H,5H-spiro[furo[2,3-f]indole-3,4'-piperidine]

Product 1

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

Procedure

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.

Workup

  1. concentrationconcentrated in vacuo
  2. extractionextracted with EtOAc (2×30 ml)
  3. extractionThe combined extract
  4. dry with materialwas dried (Na2SO4)
  5. concentrationconcentrated in vacuo
  6. customthe residue chromatographed on silica gel eluting with 1% methanol/dichloromethane

Sources & evidence

ORD record
ord-38651f313af142fcbe0fbd65902e20a6
Source dataset
uspto-grants-1999_10
Patent number
US05972951

Reaction notes

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