Dimethylformamide → 3-[2-(4-[2-Methyl-tetrazol-5-yl]phenyl)ethynyl]-3-hydroxyquinuclidine

HRID 861436Notes

Reaction equation

HRID 861436 reaction equation
[C:1]([C:3]1([OH:11])[CH:8]2[CH2:9][CH2:10][N:5]([CH2:6][CH2:7]2)[CH2:4]1)#[CH:2].[CH3:12][N:13]1[N:17]=[N:16][C:15]([C:18]2[CH:23]=[CH:22][C:21](Br)=[CH:20][CH:19]=2)=[N:14]1.C(N(CC)CC)C.CN(C)C=O>ClCCl.C1C=CC(P(C2C=CC=CC=2)C2C=CC=CC=2)=CC=1.C1C=CC(P(C2C=CC=CC=2)C2C=CC=CC=2)=CC=1.Cl[Pd]Cl.[Cu]I>[CH3:12][N:13]1[N:17]=[N:16][C:15]([C:18]2[CH:19]=[CH:20][C:21]([C:2]#[C:1][C:3]3([OH:11])[CH:8]4[CH2:9][CH2:10][N:5]([CH2:6][CH2:7]4)[CH2:4]3)=[CH:22][CH:23]=2)=[N:14]1

Participants

8

Reactant 4

HCID 6228DimethylformamideHCID 8471TriethylamineHCID 6109772-Methyl-5-(4-bromophenyl)tetrazoleHCID 36135173-Ethynyl-1-azabicyclo[2.2.2]octan-3-ol

Product 1

HCID 197031083-[2-(4-[2-Methyl-tetrazol-5-yl]phenyl)ethynyl]-3-hydroxyquinuclidineYield 42.4%

Reagents, catalysts & solvents 3

HCID 24350Copper(1+) iodide; Copper(I) iodide; Cuprous iodide; Cuprous iodide (CuI)CatalystHCID 6102075Dichlorobis(triphenylphosphine)palladiumCatalystHCID 6344DichloromethaneSolvent

Conditions

Temperature
70 °C

Procedure

A mixture of 3-ethynyl-3-hydroxyquinuclidine (0.3 g), 2-methyl-5-(4-bromophenyl)tetrazole (0.48 g), bis(triphenylphosphine)-palladium (II) chloride (70 mg), copper (I) iodide (35 mg), triethylamine (1 ml) and dimethylformamide (2 ml) was stirred at 70° C. for 2 hours. The mixture was diluted with dichloromethane (4 ml) and filtered down a short column of silica (Varian Bond-sluts S1 silica) eluting with a gradient of 0:100 (v/v) to 100:0 (v/v) methanol/dichloromethane. The appropriate organic fractions were combined, washed with saturated aqueous sodium carbonate (3×30 ml), dried (Na2CO3) and evaporated to give 3-[2-(4-[2-methyl-tetrazol-5-yl]phenyl)ethynyl]-3-hydroxyquinuclidine (260 mg) as a solid, m.p. 228°-230° C.; microanalysis, found: C, 65.9; H, 6.1; N, 22.2%; C17H19N5O requires: C, 66.0; H, 6.2; N, 22.6%; NMR: 1.2-1.4(1H,m), 1.5-1.7(1H,m), 1.8-2.0(3H,m), 2.7(4H,m), 2.8-3.2(2H,m), 4.4(3H,s), 5.6(1H,s), 7.6(2H,m), 8.05(2H,m); m/z 310(M+H).

Workup

  1. filtrationfiltered down a short column of silica (Varian Bond-sluts S1 silica)
  2. washeluting with a gradient of 0:100 (v/v) to 100:0 (v/v) methanol/dichloromethane
  3. washwashed with saturated aqueous sodium carbonate (3×30 ml)
  4. dry with materialdried (Na2CO3)
  5. customevaporated

Sources & evidence

ORD record
ord-92c8a7b240224d36b41c65613c2f468e
Source dataset
uspto-grants-1998_02
Patent number
US05714496

Reaction notes

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