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

HRID 861435

반응식

HRID 861435 반응식
[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

참가 물질

7

반응물 3

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

생성물 1

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

시약·촉매·용매 3

HCID 24350Copper(1+) iodide; Copper(I) iodide; Cuprous iodide; Cuprous iodide (CuI)촉매HCID 6102075Dichlorobis(triphenylphosphine)palladium촉매HCID 6228Dimethylformamide용매

반응 조건

온도
65 °C

실험 절차

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).

후처리

  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)

출처 및 근거

ORD 기록
ord-47dafcefd273432498f1a76304ffae4d
출처 데이터셋
uspto-grants-1998_02
특허 번호
US05714496

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