Hydrochloric Acid → HCID 11448442, compound

HRID 242353Notes

Reaction equation

HRID 242353 reaction equation
O[Li].O.[CH:4]1[C:9]([C:10]2[CH:11]=[CH:12][C:13]([F:17])=[CH:14][C:15]=2[F:16])=[CH:8][C:7]([C:18]([OH:20])=[O:19])=[C:6]([OH:21])[CH:5]=1.[CH2:22]1COCC1.Cl>CO.O>[F:16][C:15]1[CH:14]=[C:13]([F:17])[CH:12]=[CH:11][C:10]=1[C:9]1[CH:4]=[CH:5][C:6]([O:21][CH3:22])=[C:7]([C:18]([OH:20])=[O:19])[CH:8]=1

Participants

7

Reactant 4

HCID 313Hydrochloric AcidHCID 3059DiflunisalHCID 8028TetrahydrofuranHCID 168937Lithium hydroxide, monohydrate

Product 1

HCID 11448442HCID 11448442, compoundYield 93%

Reagents, catalysts & solvents 2

HCID 887MethanolSolventHCID 962WaterSolvent

Procedure

LiOH.H2O (60 mg, 1.43 mmol) was added to a solution of fully methylated diflunisal (140 mg, 0.50 mmol) in MeOH:THF:H2O (4.5 mL 1:1:1), and stirred at rt for 4 h. Upon completion, the reaction was acidified with 30% HCl, extracted with ethyl acetate (3×5 mL), dried over MgSO4 and concentrated in vacuo. The residue was purified by flash chromatography (2:1 ethyl acetate:hexane, 1% acetic acid) to afford 33 (122 mg, 93%) as a white solid. 1H NMR (CDCl3, 400 MHz) δ 10.77 (br s, 1H), 8.31 (dd, 1H, J=2.5, 0.9 Hz), 7.75 (dt, 1H, J=8.6, 2.1 Hz), 7.41 (dt, 1H, J=8.9, 6.6 Hz), 7.15 (d, 1H, J=8.8 Hz), 6.94 (m, 1H), 4.13 (s, 3H). 13C NMR (CDCl3, 100 MHz) δ 177.7, 161.4, 158.2, 135.7, 133.9, 131.4, 129.0, 123.5, 118.1, 112.2, 112.0, 104.6, 56.9. HRESIMS calculated for C14H10F2O3 (M−H) 263.0520, found 263.0514. Normal phase HPLC retention time: 21.6 min. Reverse phase HPLC retention time: 11.9 min. >99% pure.

Workup

  1. extractionextracted with ethyl acetate (3×5 mL)
  2. dry with materialdried over MgSO4
  3. concentrationconcentrated in vacuo
  4. customThe residue was purified by flash chromatography (2:1 ethyl acetate:hexane, 1% acetic acid)

Sources & evidence

ORD record
ord-d4659b4daf67408cae1f94199faf9a55
Source dataset
uspto-grants-2014_02
Patent number
US08653119B2

Reaction notes

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