Sodium Hydroxide → HCID 11347364, compound

HRID 854926Notes

Reaction equation

HRID 854926 reaction equation
[F:1][C:2]([C:5]1[CH:6]=[C:7]2[C:12](=[CH:13][CH:14]=1)[O:11][CH:10]([C:15]([F:18])([F:17])[F:16])[C:9]([C:19]([O:21]CC)=[O:20])=[CH:8]2)([F:4])[CH3:3].C1COCC1.CCO.O.[OH-].[Na+]>O>[F:1][C:2]([C:5]1[CH:6]=[C:7]2[C:12](=[CH:13][CH:14]=1)[O:11][CH:10]([C:15]([F:16])([F:17])[F:18])[C:9]([C:19]([OH:21])=[O:20])=[CH:8]2)([F:4])[CH3:3]

Participants

5

Reactant 3

HCID 14798Sodium HydroxideHCID 18504229Ethanol tetrahydrofuran waterHCID 69518523HCID 69518523, compound

Product 1

HCID 11347364HCID 11347364, compoundYield 45.1%

Reagents, catalysts & solvents 1

HCID 962WaterSolvent

Procedure

A 500 mL round bottom flask was charged with ethyl 6-(1,1-difluoroethyl)-2-(trifluoromethyl)-2H-chromene-3-carboxylate from Step 1 (0.385 g, 1.145 mmole), THF: EtOH: H2O (7:2:1 volume ratio, 3 ml), and aqueous NaOH (0.55 mL, 1.374 mmole) and stirred at r.t. for two days. The reaction was concentrated in vacuo yielding a semi-solid. The semi-solid was dissolved in water washed with diethyl ether, and the resulting aqueous phase sparged with nitrogen with warming. The resulting organic solvent-free aqueous phase was acidified with concentrated HCl solution (to pH 1) yielding a gummy solid. This mixture was extracted with ethyl acetate. The combined organics were dried over MgSO4, filtered, diluted with isooctane, and concentrated in vacuo yielding an oil. Upon standing, the oil formed a white crystalline powder (0.159 g, 45%): mp 156-158° C. (w/decomp). LCMS m/z 309 (M+H). HRMS m/z 307.0408 (M−H, C13H8F5O3, Calc'd 307.0388). 1H NMR (acetone-d6/300 MHz) 12.2-11.2 (br s, ˜0.5H (1H exch), 7.97 (s, 1H), 7.72 (s, 1H), 7.61(d d, 1H, J=8.5, 2.2 Hz), 7.13 (d, 1H, J=8.7 Hz), 5.89 (q, 1H, J=7.0 Hz), 1.97 (t, 3H, J=18.3 Hz).

Workup

  1. concentrationThe reaction was concentrated in vacuo
  2. customyielding a semi-solid
  3. washwashed with diethyl ether
  4. customthe resulting aqueous phase sparged with nitrogen
  5. temperaturewith warming
  6. customyielding a gummy solid
  7. extractionThis mixture was extracted with ethyl acetate
  8. dry with materialThe combined organics were dried over MgSO4
  9. filtrationfiltered
  10. additiondiluted with isooctane
  11. concentrationconcentrated in vacuo
  12. customyielding an oil

Sources & evidence

ORD record
ord-4117d48d163c4df68331026663c1a448
Source dataset
uspto-grants-2007_08
Patent number
US07259266B2

Reaction notes

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