1-Ethynyl-4-fluorobenzene → 2-(Benzyloxy)-4-((4-fluorophenyl)ethynyl)-5-(methoxymethoxy)pyridine

HRID 44062

反応式

HRID 44062 の反応式
[CH2:1]([O:8][C:9]1[CH:14]=[C:13](I)[C:12]([O:16][CH2:17][O:18][CH3:19])=[CH:11][N:10]=1)[C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][CH:3]=1.[C:20]([C:22]1[CH:27]=[CH:26][C:25]([F:28])=[CH:24][CH:23]=1)#[CH:21]>O1CCOCC1.[Cu]I.Cl[Pd](Cl)([P](C1C=CC=CC=1)(C1C=CC=CC=1)C1C=CC=CC=1)[P](C1C=CC=CC=1)(C1C=CC=CC=1)C1C=CC=CC=1>[CH2:1]([O:8][C:9]1[CH:14]=[C:13]([C:21]#[C:20][C:22]2[CH:27]=[CH:26][C:25]([F:28])=[CH:24][CH:23]=2)[C:12]([O:16][CH2:17][O:18][CH3:19])=[CH:11][N:10]=1)[C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][CH:3]=1

参加物

6

反応物 2

HCID 5226271-Ethynyl-4-fluorobenzeneHCID 672174582-(Benzyloxy)-4-iodo-5-(methoxymethoxy)pyridine

生成物 1

HCID 672176052-(Benzyloxy)-4-((4-fluorophenyl)ethynyl)-5-(methoxymethoxy)pyridine収率 86%

試薬・触媒・溶媒 3

HCID 24350Copper(1+) iodide; Copper(I) iodide; Cuprous iodide; Cuprous iodide (CuI)触媒HCID 178418476HCID 178418476、化合物触媒HCID 312751,4-Dioxane溶媒

反応条件

温度
80 °C

実験手順

2-(benzyloxy)-4-iodo-5-(methoxymethoxy)pyridine (3.0 g, 8.08 mmol), copper (I) iodide (92 mg, 0.485 mmol), PdCl2(PPh3)2 (284 mg, 0.404 mmol), 1-ethynyl-4-fluorobenzene (1.07 g, 8.89 mmol) were combined in dioxane (40 mL) and TEA (40 mL), degassed and stirred at 80° C. for 1.5 hrs. The mixture was diluted with EtOAc and washed with sat NaCl and H2O. The organic phase was dried over Na2SO4, filtered and concentrated and was purified on silica gel (Biotage, EtOAc/hexanes gradient, fraction collection at λ=254 nm) to give the expected product 2-(benzyloxy)-4-((4-fluorophenyl)ethynyl)-5-(methoxymethoxy)pyridine (2.52 g, 6.93 mmol, 86% yield) consistent by LCMS. LC-MS retention time: 2.71 min; m/z (MH+): 364. LC data was recorded on a Shimadzu LC-10AS liquid chromatograph equipped with a Waters SunFire 5u C18 4.6×50 mm column using a SPD-10AV UV-Vis detector at a detector wave length of 220 nM. The elution conditions employed a flow rate of 5 ml/min, a gradient of 100% solvent A/0% solvent B to 0% solvent A/100% solvent B, a gradient time of 3 min, a hold time of 1 min, and an analysis time of 4 min where solvent A was 10% acetonitrile/90% H2O/0.1% trifluoroacetic acid and solvent B was 10% H2O/90% acetonitrile/0.1% trifluoroacetic acid. MS data was determined using a Micromass Platform for LC in electrospray mode.

後処理

  1. customTEA (40 mL), degassed
  2. additionThe mixture was diluted with EtOAc
  3. washwashed
  4. dry with materialThe organic phase was dried over Na2SO4
  5. filtrationfiltered
  6. concentrationconcentrated
  7. customwas purified on silica gel (Biotage, EtOAc/hexanes gradient, fraction collection at λ=254 nm)

出典と根拠

ORDレコード
ord-5deedeaf933c4665883cc87acd154c59
出典データセット
uspto-grants-2013_09
特許番号
US08536338B2

関連ノート

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