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4-Bromo-2-methylpyridine → ethyl 4-[[4-(6-methylpyridin-3-yl)-2,2-dimethyl-(2H)-thiochromen-6-yl]-ethynyl]-benzoate

HRID 619628
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HRID 619628 반응식
Br[C:2]1[CH:7]=[CH:6][N:5]=[C:4]([CH3:8])[CH:3]=1.C([Li])(C)(C)C.[CH3:14][C:15]1([CH3:46])[CH:24]=[C:23](OS(C(F)(F)F)(=O)=O)[C:22]2[C:17](=[CH:18][CH:19]=[C:20]([C:33]#[C:34][C:35]3[CH:45]=[CH:44][C:38]([C:39]([O:41][CH2:42][CH3:43])=[O:40])=[CH:37][CH:36]=3)[CH:21]=2)[S:16]1>C1COCC1.CCCCC.[Cl-].[Cl-].[Zn+2].[Pd].C1(P(C2C=CC=CC=2)C2C=CC=CC=2)C=CC=CC=1.C1(P(C2C=CC=CC=2)C2C=CC=CC=2)C=CC=CC=1.C1(P(C2C=CC=CC=2)C2C=CC=CC=2)C=CC=CC=1.C1(P(C2C=CC=CC=2)C2C=CC=CC=2)C=CC=CC=1>[CH3:8][C:4]1[N:5]=[CH:6][C:7]([C:23]2[C:22]3[C:17](=[CH:18][CH:19]=[C:20]([C:33]#[C:34][C:35]4[CH:45]=[CH:44][C:38]([C:39]([O:41][CH2:42][CH3:43])=[O:40])=[CH:37][CH:36]=4)[CH:21]=3)[S:16][C:15]([CH3:14])([CH3:46])[CH:24]=2)=[CH:2][CH:3]=1
참가 물질실험 절차후처리출처 및 근거반응 노트

참가 물질

8

반응물 3

HCID 27628354-Bromo-2-methylpyridineHCID 10051511ethyl 4-(2,2-dimethyl-4-trifluoromethanesulfonyloxy-(2H)-thio-chromen-6-ylethynyl)-benzoate2회HCID 178418306HCID 178418306, 화합물

생성물 1

HCID 21846679ethyl 4-[[4-(6-methylpyridin-3-yl)-2,2-dimethyl-(2H)-thiochromen-6-yl]-ethynyl]-benzoate

시약·촉매·용매 4

HCID 3007855
Zincchloride
촉매
HCID 11979704Tetrakis(triphenylphosphine)palladium촉매
HCID 8003Pentane용매
HCID 8028Tetrahydrofuran용매3회

실험 절차

A solution of 4-bromo-2-methylpyridine (220.0 mg, 1.28 mmol) in 2.0 mL of THF was cooled to -78° C. and tert-butyllithium (164.0 mg, 2.56 mmol, 1.5 ml of a 1.7M solution in pentane) was added to give a red-orange solution. After 30 minutes a solution of ZnCl2 (348.0 mg, 2.56 mmol) in 4.0 mL THF was slowly added via cannula. The resulting solution was warmed to room temperature, stirred for 40 minutes, and transferred via cannula to a solution of ethyl 4-(2,2-dimethyl-4-trifluoromethanesulfonyloxy-(2H)thiochromen-6-yl-ethynyl)-benzoate (Compound 224, 172.0 mg, 0.35 mmol) and tetrakis(triphenylphosphine) palladium(0) (24.0 mg, 0.02 mmol) in 2.0 mL THF. This solution was heated to 50° C. for 2 hours, cooled to room temperature, and the reaction quenched by the addition of saturated aqueous NH4Cl. The solution was extracted with EtOAc and the combined organic layers were washed with H2O and saturated aqueous NaCl before being dried (MgSO4) and concentrated under reduced pressure. The title compound, 109.0 mg (72%) was isolated by column chromatography (5% EtOAc/hexanes) as a pale-yellow solid. 1H NMR (300 MHz, CDCl3) δ: 8.45 (1H, d, J=2.0 Hz), 8.00 (2H, d, J=8.5 Hz), 7.52 (2H, d, J=8.5 Hz), 7.49 (1H, dd, J=2.3, 8.1 Hz), 7.36 (2H, m), 7.20 (1H, d, J=8.1 Hz), 7.16 (1H, d, J=1.5 Hz), 5.86 (1H, s), 4.38 (2H, q, J=7.1 Hz), 2.63 (3H, s), 1.50 (6H, s), 1.40 (3H, t, J=7.1 Hz).

후처리

  1. customto give a red-orange solution
  2. temperatureThis solution was heated to 50° C. for 2 hours
  3. temperaturecooled to room temperature
  4. customthe reaction quenched by the addition of saturated aqueous NH4Cl
  5. extractionThe solution was extracted with EtOAc
  6. washthe combined organic layers were washed with H2O and saturated aqueous NaCl
  7. dry with materialbefore being dried (MgSO4)
  8. concentrationconcentrated under reduced pressure

출처 및 근거

ORD 기록
ord-34671293d4ce42f7958174f4900a54b2
출처 데이터셋
uspto-grants-1999_09
DOI
10.6084/m9.figshare.5104873.v1
특허 번호
US05958954

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