Nitrogen → Chromanone

HRID 1408825Notes

Reaction equation

HRID 1408825 reaction equation
[C:1]([O-:4])([O-])=O.[Cs+].[Cs+].F[C:8]1[CH:9]=[C:10](B(O)O)[CH:11]=[C:12](F)[CH:13]=1.[O:18]1CCO[CH2:20][CH2:19]1.N#N>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.O>[O:18]1[C:12]2[C:13](=[CH:8][CH:9]=[CH:10][CH:11]=2)[C:1](=[O:4])[CH2:20][CH2:19]1

Participants

7

Reactant 4

HCID 947NitrogenHCID 10796Cesium carbonateHCID 312751,4-DioxaneHCID 2734338(3,5-Difluorophenyl)boronic acid

Product 1

HCID 68110Chromanone

Reagents, catalysts & solvents 2

HCID 178418476HCID 178418476, compoundCatalystHCID 962WaterSolvent

Procedure

To a 10 mL CEM microwave test tube was charged with Cs2CO3 (391 mg, 1.20 mmol), PdCl2(PPh3)2 (30 mg, 0.04 mmol), (S/R)-6-bromo-2-((R/S)-tetrahydro-2H-pyran-3-yl)chroman-4-one (185.7 mg, 0.60 mmol), 3,5-difluorophenylboronic acid (142 mg, 0.90 mmol), dioxane (3 mL) and H2O (0.3 mL), the system was swept with N2 and capped, and heated in a CEM microwave reactor at 100 C for 8 min. Another tube charged with the same amount of reagents and starting material was repeated the same reaction at the same temperature and reaction time. Combined the reaction mixture and evaporated. The residue was dissolved in MeOH and filtered. The filtrate was evaporated and purified by flash chromatography on silica gel and eluted with EA in hexane (0-40%) to give (S/R)-6-(3,5-difluorophenyl)-2-(R/S)-tetrahydro-2H-pyran-3-yl)chroman-4-one (281 mg). 1H NMR (400 MHz, CDCl3) δ: 8.07 (s, 1H), 7.68 (dd, J=8.4, 2.0, 1H), 7.09-7.06 (m, 3H), 6.77 (m, 1H), 4.38 (m, 1H), 3.97-3.90 (m, 2H), 3.52-3.43 (m, 2H), 2.84-2.65 (m, 2H), 2.05 (m, 2H), 1.73-1.61 (m, 4H); 19F NMR (375 Hz, CDCl3) δ: −109.82; MS ESI+ve m/z 345 (M+H)+.

Workup

  1. customcapped
  2. temperatureheated in a CEM microwave reactor at 100 C for 8 min
  3. additionAnother tube charged with the same amount of reagents
  4. customthe same reaction
  5. customat the same temperature and reaction time
  6. customevaporated
  7. dissolutionThe residue was dissolved in MeOH
  8. filtrationfiltered
  9. customThe filtrate was evaporated
  10. custompurified by flash chromatography on silica gel
  11. washeluted with EA in hexane (0-40%)

Sources & evidence

ORD record
ord-a3ba6b5c66d3444d9d8995e4515c98ad
Source dataset
uspto-grants-2014_12
Patent number
US08921359B2

Reaction notes

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