Thionyl Chloride → Ethyl 7-hydroxy-3-(4-methoxyphenyl)isoxazolo[4,5-c]pyridine-6-carboxylate

HRID 2388184Notes

Reaction equation

HRID 2388184 reaction equation
COC1C=C(OC)C=CC=1C[N:6]([CH2:13][C:14]1[C:15]([C:24]2[CH:29]=[CH:28][C:27]([O:30][CH3:31])=[CH:26][CH:25]=2)=[N:16][O:17][C:18]=1[C:19](OCC)=[O:20])[CH2:7][C:8]([O:10][CH2:11][CH3:12])=[O:9].CC(C)([O-])C.[K+].S(Cl)(Cl)=O>C1COCC1.C(Cl)Cl>[OH:20][C:19]1[C:18]2[O:17][N:16]=[C:15]([C:24]3[CH:29]=[CH:28][C:27]([O:30][CH3:31])=[CH:26][CH:25]=3)[C:14]=2[CH:13]=[N:6][C:7]=1[C:8]([O:10][CH2:11][CH3:12])=[O:9]

Participants

6

Reactant 3

HCID 24386Thionyl ChlorideHCID 23665647Potassium tert-butoxideHCID 67531325HCID 67531325, compound

Product 1

HCID 67530073Ethyl 7-hydroxy-3-(4-methoxyphenyl)isoxazolo[4,5-c]pyridine-6-carboxylateYield 41.8%

Reagents, catalysts & solvents 2

HCID 6344DichloromethaneSolventHCID 8028TetrahydrofuranSolvent

Conditions

Temperature
-78 °C

Procedure

Ethyl 4-(((2,4-dimethoxybenzyl)(2-ethoxy-2-oxoethyl)amino)methyl)-3-(4-methoxyphenyl)isoxazole-5-carboxylate (13.7 g, 26.7 mmol) was dissolved in 230 mL of THF and cooled to −78° C. Potassium tert-butoxide solution (53.5 mL, 53.5 mmol, 1M in THF) was added dropwise, and the mixture was stirred for 14 hours, the cold bath allowed to evaporate spontaneously. The reaction mixture was quenched with 50 mL of 1M HCl and 300 mL of saturated ammonium chloride solution. The product was extracted with EtOAc and the organic layer was dried over MgSO4 and concentrated to give 11.4 g of crude oil. The crude intermediate was dissolved in 150 mL of CH2Cl2. Thionyl chloride (2.7 mL, 36.7 mmol) was added and the reaction mixture was stirred for 16 h. The mixture was filtered through a medium porosity funnel. The solid was rinsed twice with cold CH2Cl2 and dried under vacuum to give 3.51 g of the title compound. MS: (+) m/z 315.40 (M+1).

Workup

  1. customto evaporate spontaneously
  2. customThe reaction mixture was quenched with 50 mL of 1M HCl and 300 mL of saturated ammonium chloride solution
  3. extractionThe product was extracted with EtOAc
  4. dry with materialthe organic layer was dried over MgSO4
  5. concentrationconcentrated
  6. customto give 11.4 g of crude oil
  7. stirringthe reaction mixture was stirred for 16 h
  8. filtrationThe mixture was filtered through a medium porosity funnel
  9. washThe solid was rinsed twice with cold CH2Cl2
  10. customdried under vacuum

Sources & evidence

ORD record
ord-bd5a22a83d394c859481207c3d47b8cb
Source dataset
uspto-grants-2012_09
Patent number
US08269008B2

Reaction notes

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