Dimethylformamide → HCID 57971179, 화합물

HRID 1966365노트

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HRID 1966365 반응식
Br[C:2]1[CH:3]=[C:4]2[C:9](=[CH:10][CH:11]=1)[N:8]=[CH:7][CH:6]=[CH:5]2.[CH2:12]([O:14][CH:15]([O:18][CH2:19][CH3:20])[C:16]#[CH:17])[CH3:13].C(N(CC)CC)C.C1(P(C2C=CC=CC=2)C2C=CC=CC=2)C=CC=CC=1.CN(C)C=O>[Cu]I.C([O-])(=O)C.[Pd+2].C([O-])(=O)C>[CH2:12]([O:14][CH:15]([O:18][CH2:19][CH3:20])[C:16]#[C:17][C:2]1[CH:3]=[C:4]2[C:9](=[CH:10][CH:11]=1)[N:8]=[CH:7][CH:6]=[CH:5]2)[CH3:13]

참가 물질

8

반응물 5

HCID 6228DimethylformamideHCID 8471TriethylamineHCID 11776TriphenylphosphineHCID 662853,3-DiethoxypropyneHCID 792436-Bromoquinoline

생성물 1

HCID 57971179HCID 57971179, 화합물수율 99.5%

시약·촉매·용매 2

HCID 24350Copper(1+) iodide; Copper(I) iodide; Cuprous iodide; Cuprous iodide (CuI)촉매HCID 167845palladium(II) acetate촉매

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온도
90 °C

실험 절차

A mixture of 6-bromoquinoline (8, 2.63 g, 12.6 mmol), propargylaldehyde diethyl acetal (3.73 mL, 25.2 mmol, 2.0 equiv), triethylamine (TEA, 12.7 mL, 90.8 mmol, 7.2 equiv), copper(I) iodide (CuI, 24.0 mg, 0.126 mmol, 0.01 equiv), and triphenylphosphine (PPh3, 0.39716 g, 1.5142 mmol, 0.12 equiv) in N,N-dimethylformamide (DMF, 15.6 mL, 202 mmol) was degassed with nitrogen bubbling for 5 min. Palladium acetate (Pd(OAc)2, 0.08499 g, 0.3786 mmol, 0.03 equiv) was added and the mixture was degassed with nitrogen bubbling for 5 min. The reaction mixture was heated to 90° C. under nitrogen with stirring. After 3 h and 10 min, HPLC indicated that the reaction was complete. The reaction mixture was diluted with ethyl acetate (EtOAc, 100 mL) and washed with water (H2O, 2×100 mL). The aqueous layer was extracted with ethyl acetate (EtOAc, 20 mL). The combined organic extracts were then concentrated under the reduced pressure to give the crude product as a black oil. The crude product was purified by flash column chromatography (SiO2, 0-40% EtOAc in hexane gradient elution) to afford 6-(3,3-diethoxyprop-1-ynyl)quinoline (22, 3.2 g, 3.22 g theoretical, 99% yield) as a colorless oil. For 22: 1H NMR (400 MHz, DMSO-d6) δ ppm 8.92 (dd, 1H, J=4.35 Hz, 1.86 Hz), 8.36 (d, 1H, J=8.40 Hz, 1.66 Hz), 8.20 (d, 1H, J=1.78 Hz), 7.99 (d, 1H, J=8.71 Hz), 7.76 (dd, 1H, J=8.71 Hz, 1.87 Hz), 7.57 (dd, 1H, J=8.09 Hz, 4.05 Hz), 5.58 (s, 1H), 3.75-3.55 (m, 4H), 1.17 (t, 6H), J=7.16 Hz); C16H17NO2 (MW 255.31), LCMS (EI) m/e 256.0 (M++H).

후처리

  1. customwas degassed with nitrogen bubbling for 5 min
  2. customthe mixture was degassed with nitrogen bubbling for 5 min
  3. custom10 min, HPLC
  4. additionThe reaction mixture was diluted with ethyl acetate (EtOAc, 100 mL)
  5. washwashed with water (H2O, 2×100 mL)
  6. extractionThe aqueous layer was extracted with ethyl acetate (EtOAc, 20 mL)
  7. concentrationThe combined organic extracts were then concentrated under the reduced pressure
  8. customto give the crude product as a black oil
  9. customThe crude product was purified by flash column chromatography (SiO2, 0-40% EtOAc in hexane gradient elution)

출처 및 근거

ORD 기록
ord-39efa77161d4454dbffbfda9d0861c3f
출처 데이터셋
uspto-grants-2013_04
특허 번호
US08420645B2

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