Hydrochloric Acid → HCID 89781864, compound

HRID 1055955Notes

Reaction equation

HRID 1055955 reaction equation
Br[C:2]1[CH:11]=[CH:10][CH:9]=[C:8]2[C:3]=1[N:4]=[C:5]([F:13])[C:6]([CH3:12])=[N:7]2.C([Sn](CCCC)(CCCC)[C:19]([O:21]CC)=[CH2:20])CCC.Cl>C1C=CC([P]([Pd]([P](C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)([P](C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)[P](C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)=CC=1.C1(C)C=CC=CC=1>[F:13][C:5]1[C:6]([CH3:12])=[N:7][C:8]2[C:3]([N:4]=1)=[C:2]([C:19](=[O:21])[CH3:20])[CH:11]=[CH:10][CH:9]=2

Participants

6

Reactant 3

HCID 313Hydrochloric AcidHCID 619414Stannane, tributyl(1-ethoxyethenyl)-HCID 897819405-Bromo-3-fluoro-2-methylquinoxaline

Product 1

HCID 89781864HCID 89781864, compoundYield 63.2%

Reagents, catalysts & solvents 2

HCID 178418397HCID 178418397, compoundCatalystHCID 1140TolueneSolvent

Conditions

Temperature
90 °C

Procedure

A 1-L, three-necked round-bottomed flask equipped with a mechanical stirrer, reflux condenser, nitrogen gas inlet, and a temperature probe was charged with 5-bromo-3-fluoro-2-methylquinoxaline (30 g, 124 mmol), Pd(PPh3)4 (4.31 g, 3.73 mmol), toluene (300 mL), and tributyl(1-ethoxyvinyl)tin (Synthonix, Wake Forest, N.C.; 46.2 mL, 137 mmol), and the resulting mixture was heated under N2 atmosphere at 90° C. for 18 hours. The mixture was cooled to RT, HCl (6.0 N, aq.; 12.45 mL, 74.7 mmol) was added, and the resulting mixture was stirred at RT for 10 min. The mixture was extracted with EtOAc (500 mL). The organic layer was separated and sequentially washed with brine (2×200 mL) and saturated aq. NaHCO3 (100 mL) and then concentrated in vacuo. Chromatographic purification of the residue (silica gel, 0-100% DCM/heptane followed by repurification with silica gel, 0-75% EtOAc/heptane) furnished 1-(3-fluoro-2-methylquinoxalin-5-yl)ethanone (126 g; 16.0 g, 78.4 mmol, 63% yield) as an orange solid: 1H NMR (400 MHz, CDCl3) δ ppm 8.20 (1H, dd, J=8.3, 1.3 Hz), 8.10 (1H, dd, J=7.3, 1.1 Hz), 7.77 (1H, t, J=7.8 Hz), 2.92 (3H, s), 2.79 (3H, d, J=1.6 Hz). 19F NMR (377 MHz, CDCl3) δ ppm −69.81 (1F, s). m/z (ESI, +ve) 205.1 (M+H)+.

Workup

  1. temperaturereflux condenser, nitrogen gas inlet
  2. temperatureThe mixture was cooled to RT
  3. extractionThe mixture was extracted with EtOAc (500 mL)
  4. customThe organic layer was separated
  5. washsequentially washed with brine (2×200 mL) and saturated aq. NaHCO3 (100 mL)
  6. concentrationconcentrated in vacuo
  7. customChromatographic purification of the residue (silica gel, 0-100% DCM/heptane followed by repurification with silica gel, 0-75% EtOAc/heptane)

Sources & evidence

ORD record
ord-76e9ed604885472098901e3ab4121318
Source dataset
uspto-grants-2016_07
Patent number
US09394297B2

Reaction notes

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