Citric Acid → HCID 86681906, compound

HRID 872953Notes

Reaction equation

HRID 872953 reaction equation
[H-].[Na+].[F:3][C:4]1[CH:9]=[CH:8][C:7]([C:10]2[C:14]([CH2:15][OH:16])=[C:13]([CH3:17])[O:12][N:11]=2)=[CH:6][CH:5]=1.Cl[C:19]1[CH:26]=[CH:25][C:22]([C:23]#[N:24])=[CH:21][N:20]=1.C(O)(=O)CC(CC(O)=O)(C(O)=O)O>C1COCC1.O>[F:3][C:4]1[CH:5]=[CH:6][C:7]([C:10]2[C:14]([CH2:15][O:16][C:19]3[CH:26]=[CH:25][C:22]([C:23]#[N:24])=[CH:21][N:20]=3)=[C:13]([CH3:17])[O:12][N:11]=2)=[CH:8][CH:9]=1

Participants

7

Reactant 4

HCID 311Citric AcidHCID 24758Sodium hydrideHCID 51520946-Chloro-3-pyridinecarbonitrileHCID 28473136(3-(4-Fluorophenyl)-5-methylisoxazol-4-yl)methanol

Product 1

HCID 86681906HCID 86681906, compoundYield 97.5%

Reagents, catalysts & solvents 2

HCID 962WaterSolventHCID 8028TetrahydrofuranSolvent2×

Procedure

To a suspension of sodium hydride (60% in mineral oil, 7.9 g, 181 mmol, 1.5 eq.) in THF (65 mL) was added within 30 minutes at room temperature a solution of [3-(4-Fluorophenyl)-5-methyl-isoxazol-4-yl]-methanol (25.0 g, 121 mmol) and 6-chloronicotinonitrile (16.7 g, 121 mmol) in THF (120 mL) and the resulting mixture was stirred for one hour. A solution of citric acid (18.5 g, 96.5 mmol) in water (185 mL) was added to the reaction mixture within 30 minutes. From the resulting THF/water mixture THF was distilled off under reduced pressure at a jacket temperature of 60° C. and replaced by ethanol. In total 284 g of ethanol were added. The resulting suspension was stirred for one hour at room temperature. The crystals were filtered off, washed with a mixture of ethanol (60 mL) and water (60 mL) and subsequently dried at 50° C./<25 mbar to afford 36.5 g (91% corrected yield) of the title nitrile as an off-white solid with an assay of 93% (w/w).

Workup

  1. distillationFrom the resulting THF/water mixture THF was distilled off under reduced pressure at a jacket temperature of 60° C.
  2. additionIn total 284 g of ethanol were added
  3. stirringThe resulting suspension was stirred for one hour at room temperature
  4. filtrationThe crystals were filtered off
  5. washwashed with a mixture of ethanol (60 mL) and water (60 mL)
  6. customsubsequently dried at 50° C./<25 mbar

Sources & evidence

ORD record
ord-b2275f549c6c4a8a96d3c8c2cc960ce6
Source dataset
uspto-grants-2015_03
Patent number
US08975397B2

Reaction notes

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