Potassium Carbonate → HCID 118075445, compound

HRID 1051642Notes

Reaction equation

HRID 1051642 reaction equation
Br[C:2]1[C:3]([O:16][CH2:17][CH:18]([Cl:20])Cl)=[C:4]2[C:9](=[CH:10][CH:11]=1)[N:8]([C:12](=[O:14])[CH3:13])[C@@H:7]([CH3:15])[CH2:6][CH2:5]2.[CH:21]1([N:24]2[CH:28]=[C:27](B3OC(C)(C)C(C)(C)O3)[CH:26]=[N:25]2)[CH2:23][CH2:22]1.C(=O)([O-])[O-].[K+].[K+].O1CCOCC1>C1C=CC(P(C2C=CC=CC=2)[C-]2C=CC=C2)=CC=1.C1C=CC(P(C2C=CC=CC=2)[C-]2C=CC=C2)=CC=1.Cl[Pd]Cl.[Fe+2].O>[Cl:20]/[CH:18]=[CH:17]/[O:16][C:3]1[C:2]([C:27]2[CH:26]=[N:25][N:24]([CH:21]3[CH2:23][CH2:22]3)[CH:28]=2)=[CH:11][CH:10]=[C:9]2[C:4]=1[CH2:5][CH2:6][C@H:7]([CH3:15])[N:8]2[C:12](=[O:14])[CH3:13]

Participants

7

Reactant 4

HCID 11430Potassium CarbonateHCID 312751,4-DioxaneHCID 593271331-Cyclopropyl-4-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)-1H-pyrazoleHCID 118075859HCID 118075859, compound

Product 1

HCID 118075445HCID 118075445, compoundYield 29.3%

Reagents, catalysts & solvents 2

HCID 178418228Bis(cyclopenta-1,4-dien-1-yl(diphenyl)phosphane);dichloropalladium;iron(2+)CatalystHCID 962WaterSolvent

Conditions

Temperature
100 °C

Procedure

A 50-mL round-bottom flask was purged and maintained with an inert atmosphere of nitrogen and charged with 1-[(2S)-6-bromo-5-(2,2-dichloroethoxy)-2-methyl-1,2,3,4-tetrahydroquinolin-1-yl]ethan-1-one (43 mg, 0.11 mmol), 1-cyclopropyl-4-(tetramethyl-1,3,2-dioxaborolan-2-yl)-1H-pyrazole (40 mg, 0.17 mmol), [1,1′-bis(diphenylphosphino)ferrocene]dichloropalladium(II) (8 mg, 0.01 mmol), potassium carbonate (31 mg, 0.22 mmol), 1,4-dioxane (24 mL), and water (4 mL). The resulting mixture stirred for 15 h at 100° C. in an oil bath. After cooling to room temperature, the reaction mixture was passed a short pad of celite and concentrated under vacuum. The residue was purified by preparative thin layer chromatography (eluting with dichloromethane/methanol, 50:1 then 20:1) to afford (S,E)-1-(5-(2-chlorovinyloxy)-6-(1-cyclopropyl-1H-pyrazol-4-yl)-2-methyl-3,4-dihydroquinolin-1(2H)-yl)ethanone (12 mg, 26%) as a white solid. 1H NMR (300 MHz, CD3OD) δ ppm 1.05-1.15 (m, 7H), 1.35-1.58 (m, 1H), 2.21 (s, 3H), 2.25-2.50 (m, 2H), 2.80-2.93 (m, 1H), 3.65-3.75 (m, 1H), 4.61 (s, 1H), 4.70-4.85 (m, 1H), 5.52 (d, J=4.20 Hz, 1H), 6.52 (d, J=4.20 Hz, 1H), 7.15-7.25 (m, 1H), 7.54 (d, J=8.40 Hz, 1H), 7.89 (s, 1H), 8.07 (s, 1H). MS (ESI, pos. ion) m/z 372 [M+H]+.

Workup

  1. customA 50-mL round-bottom flask was purged
  2. temperaturemaintained with an inert atmosphere of nitrogen
  3. temperatureAfter cooling to room temperature
  4. concentrationconcentrated under vacuum
  5. customThe residue was purified by preparative thin layer chromatography (
  6. washeluting with dichloromethane/methanol, 50:1

Sources & evidence

ORD record
ord-a4f4c6acdd9845c8a5b28fb413eaab23
Source dataset
uspto-grants-2016_07
Patent number
US09388161B2

Reaction notes

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