Thionyl Chloride → HCID 67530166, compound

HRID 2388244Notes

Reaction equation

HRID 2388244 reaction equation
COC1C=C(OC)C=CC=1C[N:6]([CH2:13][C:14]1[C:15]([C:24]2(Br)[CH2:29][CH2:28][CH2:27][CH2:26][CH2:25]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].COC1C=C(OC)C=CC=1CN(CC1C(C2CCCCC=2)=NOC=1C(OCC)=O)CC(OCC)=O.CC(C)([O-])C.[K+].S(Cl)(Cl)=O>C1COCC1.C(Cl)Cl>[CH2:11]([O:10][C:8]([C:7]1[N:6]=[CH:13][C:14]2[C:15]([C:24]3[CH2:29][CH2:28][CH2:27][CH2:26][CH:25]=3)=[N:16][O:17][C:18]=2[C:19]=1[OH:20])=[O:9])[CH3:12]

Participants

7

Reactant 4

HCID 24386Thionyl ChlorideHCID 23665647Potassium tert-butoxideHCID 67529026HCID 67529026, compoundHCID 67530116HCID 67530116, compound

Product 1

HCID 67530166HCID 67530166, compound

Reagents, catalysts & solvents 2

HCID 6344DichloromethaneSolventHCID 8028TetrahydrofuranSolvent

Conditions

Temperature
-78 °C

Procedure

The above mixture of ethyl 4-(((2,4-dimethoxybenzyl)(2-ethoxy-2-oxoethyl)amino)-methyl)-3-(1-bromo-cyclohexyl)-isoxazole-5-carboxylate and ethyl 4-(((2,4-dimethoxybenzyl)(2-ethoxy-2-oxoethyl)amino)methyl)-3-(1-cyclohexenyl)-isoxazole-5-carboxylate was dissolved in 40 mL of THF and cooled to −78° C. Potassium tert-butoxide solution (6.9 mL, 6.9 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 cooled in an ice bath and quenched with 20 mL of 1M HCl. The product was extracted with EtOAc and the organic layer was dried over MgSO4 and concentrated to give 0.8 g of crude oil. The crude intermediate was dissolved in 12 mL of CH2Cl2. Thionyl chloride (0.2 mL, 2.73 mmol) was added and the reaction mixture was stirred for 5 h at ambient temperature. The volatiles were evaporated and the residue was partitioned between CH2Cl2 (50 mL) and saturated sodium bicarbonate solution (50 mL). To the vigorously stirring biphasic mixture was added 4M hydrochloric acid until pH was 2. The aqueous layer was extracted with additional CH2Cl2 and the combined organic layer was dried over MgSO4 and concentrated. The crude residue was purified by chromatography (0-100% CH2Cl2/hexanes) to give 210 mg of the title compound. MS: (+) m/z 289.30 (M+1).

Workup

  1. customto evaporate spontaneously
  2. temperatureThe reaction mixture was cooled in an ice bath
  3. customquenched with 20 mL of 1M HCl
  4. extractionThe product was extracted with EtOAc
  5. dry with materialthe organic layer was dried over MgSO4
  6. concentrationconcentrated
  7. customto give 0.8 g of crude oil
  8. stirringthe reaction mixture was stirred for 5 h at ambient temperature
  9. customThe volatiles were evaporated
  10. customthe residue was partitioned between CH2Cl2 (50 mL) and saturated sodium bicarbonate solution (50 mL)
  11. stirringTo the vigorously stirring biphasic mixture
  12. additionwas added 4M hydrochloric acid until pH was 2
  13. extractionThe aqueous layer was extracted with additional CH2Cl2
  14. dry with materialthe combined organic layer was dried over MgSO4
  15. concentrationconcentrated
  16. customThe crude residue was purified by chromatography (0-100% CH2Cl2/hexanes)

Sources & evidence

ORD record
ord-0d7b8937bb2a4d8fb77a84ae04f5bf3d
Source dataset
uspto-grants-2012_09
Patent number
US08269008B2

Reaction notes

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