Dimethylformamide → HCID 57971179, compound

HRID 1966365Notes

Reaction equation

HRID 1966365 reaction equation
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]

Participants

8

Reactant 5

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

Product 1

HCID 57971179HCID 57971179, compoundYield 99.5%

Reagents, catalysts & solvents 2

HCID 24350Copper(1+) iodide; Copper(I) iodide; Cuprous iodide; Cuprous iodide (CuI)CatalystHCID 167845palladium(II) acetateCatalyst

Conditions

Temperature
90 °C

Procedure

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).

Workup

  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)

Sources & evidence

ORD record
ord-39efa77161d4454dbffbfda9d0861c3f
Source dataset
uspto-grants-2013_04
Patent number
US08420645B2

Reaction notes

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