Toluene → HCID 89782323, compound

HRID 1055915Notes

Reaction equation

HRID 1055915 reaction equation
C([Sn](CCCC)(CCCC)[C:6]([O:8]CC)=[CH2:7])CCC.Br[C:20]1[CH:21]=[CH:22][CH:23]=[C:24]2[C:29]=1[N:28]=[C:27]([C:30]([N:32]1[CH2:37][CH2:36][O:35][CH2:34][CH2:33]1)=[O:31])[CH:26]=[CH:25]2.C1(C)C=CC=CC=1.C(OC=C)=C>C1COCC1.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.CCOC(C)=O.CC(C)=O>[N:32]1([C:30]([C:27]2[CH:26]=[CH:25][C:24]3[C:29](=[C:20]([C:6](=[O:8])[CH3:7])[CH:21]=[CH:22][CH:23]=3)[N:28]=2)=[O:31])[CH2:37][CH2:36][O:35][CH2:34][CH2:33]1

Participants

10

Reactant 4

HCID 1140TolueneHCID 8024Vinyl ether2×HCID 619414Stannane, tributyl(1-ethoxyethenyl)-HCID 89781987HCID 89781987, compound

Product 1

HCID 89782323HCID 89782323, compoundYield 92.3%

Reagents, catalysts & solvents 5

HCID 313Hydrochloric AcidCatalystHCID 178418397HCID 178418397, compoundCatalystHCID 180AcetoneSolvent2×HCID 8028TetrahydrofuranSolventHCID 8857Ethyl AcetateSolvent

Conditions

Temperature
100 °C

Procedure

A mixture of Pd(PPh3)4 (18 mg, 0.016 mmol), tributyl(1-ethoxyvinyl)stannane (0.12 mL, 0.34 mmol), (8-bromoquinolin-2-yl)(morpholino)methanone (Example 167a; 100 mg, 0.31 mmol), and toluene (1.5 mL) were stirred in a sealed 5 mL glass microwave tube under argon at 100° C. for 63 h. Formation of both the vinyl ether (M+1=313.1) and the methyl ketone (M+1=285.0) were detected by LCMS. The mixture was concentrated under reduced pressure, and the residue was adsorbed onto silica gel. Chromatographic purification (silica gel, 10-70% EtOAc in hexanes) afforded a mixture of the vinyl ether and the methyl ketone as a colorless oil. The material was dissolved in THF (3 mL), the solution was cooled to 0° C., 2 drops of 1N HCl were added and the solution was stirred at 0° C. for 5 min. EtOAc (25 mL) was added to the reaction mixture and the solution was washed successively with 1N NaOH (5 mL), water (10 mL) and brine (10 mL). The combined aq. washes were extracted with 25% IPA in CHCl3, and all organic layers were then combined, dried over MgSO4, filtered, and concentrated in vacuo to give 1-(2-(morpholine-4-carbonyl)quinolin-8-yl)ethanone (81.4 mg, 0.286 mmol, 92% yield) as a white film: 1H NMR (400 MHz, DMSO-d6) δ ppm 8.62 (d, J=8.6 Hz, 1H), 8.18-8.24 (m, 1H), 7.95 (dd, J=7.1, 1.3 Hz, 1H), 7.72-7.83 (m, 2H), 3.72 (s, 4H), 3.56 (d, J=4.7 Hz, 4H), 2.79 (s, 3H). m/z (ESI, +ve ion) 285.0 (M+H)+.

Workup

  1. concentrationThe mixture was concentrated under reduced pressure
  2. customChromatographic purification (silica gel, 10-70% EtOAc in hexanes)
  3. customafforded
  4. temperaturethe solution was cooled to 0° C.
  5. stirringthe solution was stirred at 0° C. for 5 min
  6. washthe solution was washed successively with 1N NaOH (5 mL), water (10 mL) and brine (10 mL)
  7. extractionThe combined aq. washes were extracted with 25% IPA in CHCl3
  8. dry with materialdried over MgSO4
  9. filtrationfiltered
  10. concentrationconcentrated in vacuo

Sources & evidence

ORD record
ord-292c110d19e344fc9c28df614f502aee
Source dataset
uspto-grants-2016_07
Patent number
US09394297B2

Reaction notes

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