Tetrahydrofuran → HCID 66879735, compound

HRID 1913599Notes

Reaction equation

HRID 1913599 reaction equation
O[C:2]1[CH:7]=[CH:6][C:5]([C:8]([F:11])([F:10])[F:9])=[CH:4][C:3]=1[NH:12][C:13](=[O:20])[C:14]1[CH:19]=[CH:18][N:17]=[CH:16][CH:15]=1.O1CCCC1.C1(P(C2C=CC=CC=2)C2C=CC=CC=2)C=CC=CC=1.N(C(OCC)=O)=NC(OCC)=O>O.C1(C)C=CC=CC=1>[N:17]1[CH:16]=[CH:15][C:14]([C:13]2[O:20][C:2]3[CH:7]=[CH:6][C:5]([C:8]([F:9])([F:10])[F:11])=[CH:4][C:3]=3[N:12]=2)=[CH:19][CH:18]=1

Participants

7

Reactant 4

HCID 8028TetrahydrofuranHCID 11776Triphenylphosphine2×HCID 220568ethyl N-ethoxycarbonyliminocarbamate2×HCID 66879863HCID 66879863, compound

Product 1

HCID 66879735HCID 66879735, compoundYield 27.8%

Reagents, catalysts & solvents 2

HCID 962WaterSolventHCID 1140TolueneSolvent2×

Procedure

To a mixture of 1.69 g of N-(2-hydroxy-5-trifluoromethylphenyl)isonicotinamide, 25 ml of tetrahydrofuran and 2.36 g of triphenylphosphine, 3.91 g of 40% toluene solution of diethyl azodicarboxylate was added dropwise at room temperature. After 1.3 hours, 0.6 g of triphenylphosphine and 1.0 g of 40% toluene solution of diethyl azodicarboxylate were added and stirred for further 40 minutes. Water was poured into the mixture, followed by extraction with ethyl acetate twice. The combined organic layers were washed with water and a saturated sodium chloride solution, dried over sodium sulfate, and then concentrated under reduced pressure. The residue was washed with diethyl ether, and 10 ml of methanol and 10 ml of 1 M aqueous solution of sodium hydroxide were added and stirred for two hours at room temperature. After concentrated hydrochloric acid was added to the reaction mixture while ice-cooling so as to make it acidic, the reaction mixture was washed with ethyl acetate. To the aqueous layer, 1 M aqueous solution of sodium hydroxide was added so as to make the solution alkaline, followed by extraction with ethyl acetate twice. The combined organic layers were washed with water and a saturated sodium chloride solution, and dried over magnesium sulfate and then concentrated under reduced pressure. The residue was subjected to silica gel column chromatography to give 0.44 g of 2-(pyridin-4-yl)-5-(trifluoromethyl)benzoxazole (hereinafter, referred to as “active compound 13”).

Workup

  1. additionwas added dropwise at room temperature
  2. extractionfollowed by extraction with ethyl acetate twice
  3. washThe combined organic layers were washed with water
  4. dry with materiala saturated sodium chloride solution, dried over sodium sulfate
  5. concentrationconcentrated under reduced pressure
  6. washThe residue was washed with diethyl ether, and 10 ml of methanol and 10 ml of 1 M aqueous solution of sodium hydroxide
  7. additionwere added
  8. stirringstirred for two hours at room temperature
  9. additionAfter concentrated hydrochloric acid was added to the reaction mixture while ice-
  10. temperaturecooling so as
  11. washthe reaction mixture was washed with ethyl acetate
  12. additionTo the aqueous layer, 1 M aqueous solution of sodium hydroxide was added so as
  13. extractionfollowed by extraction with ethyl acetate twice
  14. washThe combined organic layers were washed with water
  15. dry with materiala saturated sodium chloride solution, and dried over magnesium sulfate
  16. concentrationconcentrated under reduced pressure

Sources & evidence

ORD record
ord-cb3c8be12356425dac85b30041575482
Source dataset
uspto-grants-2013_12
Patent number
US08609705B2

Reaction notes

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