Nitrogen → 6-Bromo-2-((4-fluorophenyl)ethynyl)pyridin-3-yl acetate

HRID 44058

반응식

HRID 44058 반응식
[C:1]([O:4][C:5]1[C:6](I)=[N:7][C:8]([Br:11])=[CH:9][CH:10]=1)(=[O:3])[CH3:2].[C:13]([C:15]1[CH:20]=[CH:19][C:18]([F:21])=[CH:17][CH:16]=1)#[CH:14].N#N>C(N(CC)CC)C.[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>[C:1]([O:4][C:5]1[C:6]([C:14]#[C:13][C:15]2[CH:20]=[CH:19][C:18]([F:21])=[CH:17][CH:16]=2)=[N:7][C:8]([Br:11])=[CH:9][CH:10]=1)(=[O:3])[CH3:2]

참가 물질

7

반응물 3

HCID 947NitrogenHCID 5226271-Ethynyl-4-fluorobenzeneHCID 866399576-Bromo-2-iodopyridin-3-yl acetate

생성물 1

HCID 866399586-Bromo-2-((4-fluorophenyl)ethynyl)pyridin-3-yl acetate수율 73.4%

시약·촉매·용매 3

HCID 24350Copper(1+) iodide; Copper(I) iodide; Cuprous iodide; Cuprous iodide (CuI)촉매HCID 178418476HCID 178418476, 화합물촉매HCID 8471Triethylamine용매

반응 조건

온도
85 °C

실험 절차

6-bromo-2-iodopyridin-3-yl acetate (3.50 g, 10.24 mmol), 1-ethynyl-4-fluorobenzene (1.11 g, 9.21 mmol), copper (I) iodide (117 mg, 0.614 mmol), trans-dichlorobis(triphenylphosphine)palladium (II) (359 mg, 0.512 mmol) were combined and evacuated/backfilled with N2 (3×) then diluted with triethylamine (100 ml) and heated to 85° C. for 2 hours. The solvent was evaporated and the reaction was dissolved in EtOAc. The organic phase was washed with water (50 mL) and brine, dried over Na2SO4, filtered, and concentrated and was purified on silica gel (Biotage, EtOAc/hexanes gradient, fraction collection at 2, =254 nm) to give the expected product 6-bromo-2-((4-fluorophenyl)ethynyl)pyridin-3-yl acetate (2.26 g, 6.76 mmol, 66.1% yield) consistent by NMR. 1H NMR (400 MHz, DMSO-d6) δ ppm 7.77 (2H, s), 7.70 (2H, dd, J=8.78, 5.52 Hz), 7.34 (2H, t, J=8.91 Hz), 2.41 (3 H, s). LC-MS retention time: 2.18 min; m/z: parent ion not observed, —Ac: 292, 294. 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.

후처리

  1. customThe solvent was evaporated
  2. dissolutionthe reaction was dissolved in EtOAc
  3. washThe organic phase was washed with water (50 mL) and brine
  4. dry with materialdried over Na2SO4
  5. filtrationfiltered
  6. concentrationconcentrated
  7. customwas purified on silica gel (Biotage, EtOAc/hexanes gradient, fraction collection at 2, =254 nm)

출처 및 근거

ORD 기록
ord-00a1a78d277943899980f89412bac009
출처 데이터셋
uspto-grants-2013_09
특허 번호
US08536338B2

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