Sodium hydride → 2,7-Difluoro-3,6-bis[(2-methoxyethoxy)methoxy]-9h-xanthen-9-one

HRID 2357124Notes

Reaction equation

HRID 2357124 reaction equation
[F:1][C:2]1[C:15]([OH:16])=[CH:14][C:13]2[O:12][C:11]3[C:6](=[CH:7][C:8]([F:18])=[C:9]([OH:17])[CH:10]=3)[C:5](=[O:19])[C:4]=2[CH:3]=1.[H-].[Na+].[CH3:22][O:23][CH2:24][CH2:25][O:26][CH2:27]Cl>C1COCC1>[F:1][C:2]1[C:15]([O:16][CH2:22][O:23][CH2:24][CH2:25][O:26][CH3:27])=[CH:14][C:13]2[O:12][C:11]3[C:6](=[CH:7][C:8]([F:18])=[C:9]([O:17][CH2:22][O:23][CH2:24][CH2:25][O:26][CH3:27])[CH:10]=3)[C:5](=[O:19])[C:4]=2[CH:3]=1

Participants

5

Reactant 3

HCID 24758Sodium hydrideHCID 775901-(Chloromethoxy)-2-methoxyethaneHCID 121607692,7-Difluoro-3,6-dihydroxyxanthone

Product 1

HCID 593856782,7-Difluoro-3,6-bis[(2-methoxyethoxy)methoxy]-9h-xanthen-9-oneYield 65%

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent

Conditions

Temperature
0 °C

Procedure

A cloudy solution of 8 (2.4 g, 9.1 mmol) in dry THF (50 mL) was treated with sodium hydride (1.1 g, 45.8 mmol) at 0° C. under an Ar atmosphere. The mixture was stirred at 0° C. for 30 min and then 2-methoxyethoxymethyl chloride (5.2 mL, 45.8 mmol) was added. The mixture was stirred at 0° C. for an additional 30 min and then warmed to room temperature overnight. The reaction mixture was cooled to 0° C., quenched with 1M citric acid (50 mL), and then extracted with EtOAc. The combined organic layers were washed with brine, dried over Na2SO4 and concentrated in vacuo. The crude product was purified by flash column chromatography, eluting with CH2Cl2/hexane/EtOAc=1:1:0.4 to yield 2.6 g (65%) of 9 as a white solid. Rf=0.47 (in CH2Cl2/hexane/EtOAc=1:1:0.4); 1H NMR (300 MHz, CDCl3) δ7.91 (d, 2H, J=10.6 Hz), 7.28 (d, 2H, J=6.5 Hz), 5.46 (s, 4H), 3.91 (m, 4H), 3.60 (m, 4H), 3.39 (s, 6H); 13C NMR (75 MHz, CDCl3) 6174.4, 153.3, 153.2, 151.4, 151.0, 150.9, 148.2, 115.2, 115.1, 111.8, 111.6, 104.8, 94.2, 71.3, 68.6, 59.0; 19F NMR (282 MHz, CDCl3) δ −137.0 (dd, 2 F); mass spectrum, calculated for C21H22F2O8 (MH+) 441.1, Found 441.0.

Workup

  1. stirringThe mixture was stirred at 0° C. for an additional 30 min
  2. temperaturewarmed to room temperature overnight
  3. temperatureThe reaction mixture was cooled to 0° C.
  4. customquenched with 1M citric acid (50 mL)
  5. extractionextracted with EtOAc
  6. washThe combined organic layers were washed with brine
  7. dry with materialdried over Na2SO4
  8. concentrationconcentrated in vacuo
  9. customThe crude product was purified by flash column chromatography
  10. washeluting with CH2Cl2/hexane/EtOAc=1:1:0.4

Sources & evidence

ORD record
ord-3c0a3f815e9c494b89a6f5de737a8860
Source dataset
uspto-grants-2010_07
Patent number
US07759459B2

Reaction notes

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