Thionyl Chloride → HCID 67531020, compound

HRID 2388205Notes

Reaction equation

HRID 2388205 reaction equation
[Br:1][C:2]1[O:6][C:5]([C:7]2[C:11]([CH2:12][N:13](CC3C=CC(OC)=CC=3OC)[CH2:14][C:15]([O:17][CH2:18][CH3:19])=[O:16])=[C:10]([C:31]([O:33]CC)=O)[O:9][N:8]=2)=[CH:4][CH:3]=1.CC(C)([O-])C.[K+].S(Cl)(Cl)=O>C1COCC1.C(Cl)Cl>[Br:1][C:2]1[O:6][C:5]([C:7]2[C:11]3[CH:12]=[N:13][C:14]([C:15]([O:17][CH2:18][CH3:19])=[O:16])=[C:31]([OH:33])[C:10]=3[O:9][N:8]=2)=[CH:4][CH:3]=1

Participants

6

Reactant 3

HCID 24386Thionyl ChlorideHCID 23665647Potassium tert-butoxideHCID 67530545HCID 67530545, compound

Product 1

HCID 67531020HCID 67531020, compoundYield 6.4%

Reagents, catalysts & solvents 2

HCID 6344DichloromethaneSolventHCID 8028TetrahydrofuranSolvent

Conditions

Temperature
-78 °C

Procedure

Ethyl 3-(5-bromofuran-2-yl)-4-(((2,4-dimethoxybenzyl)(2-ethoxy-2-oxoethyl)amino)methyl)isoxazole-5-carboxylate (1.53 g, 2.78 mmol) was dissolved in 30 mL of THF and cooled to −78° C. Potassium tert-butoxide solution (5.6 mL, 5.55 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 5 mL of 1M HCl and 100 mL of saturated ammonium chloride solution. The product was extracted with EtOAc and the organic layer was dried over MgSO4 and concentrated to give 1.32 g of crude oil. The crude intermediate was dissolved in 15 mL of CH2Cl2. Thionyl chloride (0.29 mL, 3.92 mmol) was added and the reaction mixture was stirred for 4 h. The mixture was filtered through a medium porosity funnel. The solid was rinsed three times with cold CH2Cl2 and dried under vacuum to give 63 mg of the title compound. The filtrate was concentrated and the residue was partitioned between EtOAc and saturated sodium bicarbonate solution. The aqueous layer was extracted with additional EtOAc and the combined organic layer was dried over MgSO4 and concentrated. The residue was purified by flash chromatography (0-40% EtOAc/hexanes) to give additional 443 mg of the title compound. δ=11.4 (s, 1H), 8.98 (s, 1H), 7.20-7.24 (m, 1H), 6.58-6.65 (m, 1H), 4.61 (q, 2H, J=7.0 Hz), 1.55 (t, 3H, J=7.0 Hz).

Workup

  1. customto evaporate spontaneously
  2. customThe reaction mixture was quenched with 5 mL of 1M HCl and 100 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 1.32 g of crude oil
  7. stirringthe reaction mixture was stirred for 4 h
  8. filtrationThe mixture was filtered through a medium porosity funnel
  9. washThe solid was rinsed three times with cold CH2Cl2
  10. customdried under vacuum

Sources & evidence

ORD record
ord-86f78f73c0ad43308d49f3a17255f65e
Source dataset
uspto-grants-2012_09
Patent number
US08269008B2

Reaction notes

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