Sodium hydride → HCID 58934836, compound

HRID 855140Notes

Reaction equation

HRID 855140 reaction equation
[Cl:1][C:2]1[CH:3]=[C:4]2[C:9](=[CH:10][C:11]=1F)[O:8][CH:7]([C:13]([F:16])([F:15])[F:14])[C:6]([C:17]([O:19][CH2:20][CH3:21])=[O:18])=[CH:5]2.CS(CCO)(=O)=[O:24].[H-].[Na+]>CN(C=O)C>[Cl:1][C:2]1[CH:3]=[C:4]2[C:9](=[CH:10][C:11]=1[OH:24])[O:8][CH:7]([C:13]([F:16])([F:15])[F:14])[C:6]([C:17]([O:19][CH2:20][CH3:21])=[O:18])=[CH:5]2

Participants

5

Reactant 3

HCID 24758Sodium hydrideHCID 848342-(Methylsulfonyl)ethanolHCID 21883602ethyl 6-chloro-7-fluoro-2-(trifluoromethyl)-2H-chromene-3-carboxylate

Product 1

HCID 58934836HCID 58934836, compound

Reagents, catalysts & solvents 1

HCID 6228DimethylformamideSolvent

Conditions

Temperature
0 °C

Procedure

To the mixture of ethyl 6-chloro-7-fluoro-2-(trifluoromethyl)-2H-chromene-3-carboxylate (6 g, 18.5 mmol) and 2-(methylsulfonyl)ethanol (3.45 g, 27.7 mmol) in 125 mL of anhydrous DMF at 0° C. was added sodium hydride (60%, 2.22 g, 55.5 mmol) slowly. After stirring at 0° C. for 45 min, LCMS indicated that majority of starting material was gone. The reaction was warmed to room temperature, and stirred for another 20 min. The reaction was dumped into a dilute hydrochloric acid/ice mixture with vigorously stirring. The product was then extracted with EtOAc. The resulting organic phase was washed with brine, dried over anhydrous magnesium sulfate. After removing the solvent, the residue was purified on silica gel column with 1:1 EtOAc/hexane containing 1% HOAc. The desired product was obtained as a green yellowish solid, 1.0 g (16.7%). M.P.=118.0-125.0° C. 1H NMR(CDCl3/400 MHz) 7.61(s, 1H), 7.18(s, 1H), 6.66(s, 1H), 5.65(q, 1H, J=6.8 Hz), 4.30(m, 2H), 1.33(t, 3H, J=7.2 Hz). 13C NMR(CDCl3/400 MHz) 164.1, 155.2, 153.8, 136.0, 129.3, 123.5(q, J=287.7 Hz), 115.1, 114.1, 113.6, 104.5, 71 .0(q, J=33.2 Hz), 61.7, 14.4. 19F NMR(CDCl3/400 MHz) −78.9(d, J=6.8 Hz). LC-MS (ES+) 323.7 (M+H, 80%), 295.2(M−27, 100%). HRMS (EI+) m/z calcd for (C13H10ClF3O4) 322.0220, found 322.0231.

Workup

  1. temperatureThe reaction was warmed to room temperature
  2. stirringstirred for another 20 min
  3. stirringwith vigorously stirring
  4. extractionThe product was then extracted with EtOAc
  5. washThe resulting organic phase was washed with brine
  6. dry with materialdried over anhydrous magnesium sulfate
  7. customAfter removing the solvent
  8. customthe residue was purified on silica gel column with 1:1 EtOAc/hexane containing 1% HOAc

Sources & evidence

ORD record
ord-ff6eb63e44e84b7da1fe567623f602e8
Source dataset
uspto-grants-2007_08
Patent number
US07259266B2

Reaction notes

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