Triethylamine → 3-[2-(4-[1,3,4-Oxadiazol-2-yl]phenyl)ethynyl]-3-hydroxyquinuclidine

HRID 861435

Reaction equation

HRID 861435 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].Br[C:13]1[CH:18]=[CH:17][C:16]([C:19]2[O:20][CH:21]=[N:22][N:23]=2)=[CH:15][CH:14]=1.C(N(CC)CC)C>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.CN(C)C=O>[O:20]1[CH:21]=[N:22][N:23]=[C:19]1[C:16]1[CH:17]=[CH:18][C:13]([C:2]#[C:1][C:3]2([OH:11])[CH:8]3[CH2:9][CH2:10][N:5]([CH2:6][CH2:7]3)[CH2:4]2)=[CH:14][CH:15]=1

Participants

7

Reactant 3

HCID 8471TriethylamineHCID 7151202-(4-Bromophenyl)-1,3,4-oxadiazoleHCID 36135173-Ethynyl-1-azabicyclo[2.2.2]octan-3-ol

Product 1

HCID 197031383-[2-(4-[1,3,4-Oxadiazol-2-yl]phenyl)ethynyl]-3-hydroxyquinuclidineYield 39.2%

Reagents, catalysts & solvents 3

HCID 24350Copper(1+) iodide; Copper(I) iodide; Cuprous iodide; Cuprous iodide (CuI)CatalystHCID 6102075Dichlorobis(triphenylphosphine)palladiumCatalystHCID 6228DimethylformamideSolvent

Conditions

Temperature
65 °C

Procedure

A mixture of 3-ethynyl-3-hydroxyquinuclidine (1.06 g), 2-(4-bromopbenyl)-1,3,4-oxadiazole (1.58 g), bis(triphenylphosphine)palladium (II) chloride (245 mg), copper (I) iodide (123 mg), triethylamine (7 ml) and dimethylformamide (14 ml) were heated at 65° C. under an atmosphere of argon for 4 hours. The triethylamine and DHF were removed by evaporation. An aqueous solution of sodium hydroxide (2M, 20 ml) was added to the residue and the mixture extracted with dichloromethane (3×30 ml). The organic extracts were combined, dried (MgSO4) and evaporated. The residue was purified by flash column chromatography on silica gel eluting with 10% methanol in dichloromethane containing 1% ammonia (density 0.88 g/cm3) to give 3-[2-(4-[1,3,4-oxadiazol-2-yl]phenyl)ethynyl]-3-hydroxyquinuclidine (811 mg) as a solid, m.p. 229-230%; microanalysis, found: C, 67.9; H, 5.8; N, 14.2%; C17H17N3O3. 0.4 H2O requires: C, 67.5; H, 5.9; N, 13.9; NMR: 1.20-1.44(1H,m), 1.50-1.71(1H,m), 1.77-2.04(3H,m), 2.69(4H,t), 2.79-2.94(1H,d), 3.04-3.20(1H,d), 5.69(1H,s), 7.63(2H,d), 8.03(2H,d), 9.35(1H,s); m/z 296(M+H).

Workup

  1. customThe triethylamine and DHF were removed by evaporation
  2. additionAn aqueous solution of sodium hydroxide (2M, 20 ml) was added to the residue
  3. extractionthe mixture extracted with dichloromethane (3×30 ml)
  4. dry with materialdried (MgSO4)
  5. customevaporated
  6. customThe residue was purified by flash column chromatography on silica gel eluting with 10% methanol in dichloromethane containing 1% ammonia (density 0.88 g/cm3)

Sources & evidence

ORD record
ord-47dafcefd273432498f1a76304ffae4d
Source dataset
uspto-grants-1998_02
Patent number
US05714496

Linked notes

Loading…