Sodium Bicarbonate → HCID 118075376, compound

HRID 1051611Notes

Reaction equation

HRID 1051611 reaction equation
Br[C:2]1[C:3]([O:16][C:17]2[CH:22]=[CH:21][CH:20]=[CH:19][CH:18]=2)=[C:4]2[C:9](=[CH:10][CH:11]=1)[N:8]([C:12](=[O:14])[CH3:13])[CH:7]([CH3:15])[CH2:6][CH2:5]2.[CH3:23][S:24]([C:27]1[CH:32]=[CH:31][C:30](B(O)O)=[CH:29][CH:28]=1)(=[O:26])=[O:25].C(=O)(O)[O-].[Na+]>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.O1CCOCC1>[CH3:15][CH:7]1[CH2:6][CH2:5][C:4]2[C:9](=[CH:10][CH:11]=[C:2]([C:30]3[CH:31]=[CH:32][C:27]([S:24]([CH3:23])(=[O:26])=[O:25])=[CH:28][CH:29]=3)[C:3]=2[O:16][C:17]2[CH:22]=[CH:21][CH:20]=[CH:19][CH:18]=2)[N:8]1[C:12](=[O:14])[CH3:13]

Participants

6

Reactant 3

HCID 516892Sodium BicarbonateHCID 27343644-(Methanesulfonyl)phenylboronic acidHCID 118075637HCID 118075637, compound

Product 1

HCID 118075376HCID 118075376, compound

Reagents, catalysts & solvents 2

HCID 178418476HCID 178418476, compoundCatalystHCID 312751,4-DioxaneSolvent

Conditions

Temperature
80 °C

Procedure

A screw-cap vial equipped with a magnetic stir bar was charged with rac-1-(6-bromo-2-methyl-5-phenoxy-3,4-dihydroquinolin-1(2H)-yl)ethanone (0.024 g, 0.067 mmol), 4-(methylsulfonyl)phenylboronic acid (0.020 g, 0.100 mmol), 1,4-dioxane (0.67 mL), 1.0 M aqueous sodium bicarbonate (0.200 mL, 0.200 mmol), and bis(triphenylphosphine)palladium(II) chloride (4.7 mg, 6.7 μmol). The vial was flushed with nitrogen and then capped. The reaction mixture was then heated to 80° C. for 3 h and then cooled to room temperature. The reaction mixture was diluted with 5% aqueous sodium chloride solution (0.5 mL) and ethyl acetate. The layers were separated, and the aqueous layer was extracted with ethyl acetate. The combined extracts were concentrated under reduced pressure to afford a dark brown residue, which was then purified by preparative thin layer chromatography (1×1000 micron plate; eluting with 3:2 ethyl acetate-hexanes). The major band was isolated (26 mg) and further purified by preparative HPLC to afford rac-1-(2-methyl-6-(4-(methylsulfonyl)phenyl)-5-phenoxy-3,4-dihydroquinolin-1(2H)-yl)ethanone. 1H NMR (400 MHz, CDCl3) δ ppm 1.17 (d, J=6.60 Hz, 3H), 1.45 (br s, 1H), 2.07-2.24 (m, 1H), 2.27 (s, 3H), 2.29-2.37 (m, 1H), 2.71 (dt, J=16.13, 6.42 Hz, 1H), 3.01 (s, 3H), 4.79 (br s, 1H), 6.59-6.69 (m, 2H), 6.82-6.95 (m, 1H), 7.15 (t, J=7.70 Hz, 2H), 7.32 (br d, J=7.33 Hz, 2H), 7.65 (d, J=8.43 Hz, 2H), 7.84 (d, J=8.43 Hz, 2H). MS (ESI, pos. ion) m/z 436 [M+H]+.

Workup

  1. customA screw-cap vial equipped with a magnetic stir bar
  2. customThe vial was flushed with nitrogen
  3. customcapped
  4. temperaturecooled to room temperature
  5. additionThe reaction mixture was diluted with 5% aqueous sodium chloride solution (0.5 mL) and ethyl acetate
  6. customThe layers were separated
  7. extractionthe aqueous layer was extracted with ethyl acetate
  8. concentrationThe combined extracts were concentrated under reduced pressure
  9. customto afford a dark brown residue, which
  10. customwas then purified by preparative thin layer chromatography (1×1000 micron plate; eluting with 3:2 ethyl acetate-hexanes)
  11. customThe major band was isolated (26 mg)
  12. customfurther purified by preparative HPLC

Sources & evidence

ORD record
ord-8f6b65f69fb9431bab37f68702a63377
Source dataset
uspto-grants-2016_07
Patent number
US09388161B2

Reaction notes

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