Dichloromethane → 6-[2-(5-Chloro-2,4-dimethoxy-phenyl)ethyl]-6-cyclopentyl-tetrahydropyran-2,4-dione

HRID 858729Notes

Reaction equation

HRID 858729 reaction equation
[CH3:1][O:2][C:3]1[CH:8]=[C:7]([O:9][CH3:10])[CH:6]=[CH:5][C:4]=1[CH2:11][CH2:12][C:13]1([CH:21]2[CH2:25][CH2:24][CH2:23][CH2:22]2)[O:18][C:17](=[O:19])[CH2:16][C:15](=[O:20])[CH2:14]1.C([O-])(O)=O.[Na+].C(Cl)[Cl:32]>>[Cl:32][C:6]1[C:7]([O:9][CH3:10])=[CH:8][C:3]([O:2][CH3:1])=[C:4]([CH2:11][CH2:12][C:13]2([CH:21]3[CH2:25][CH2:24][CH2:23][CH2:22]3)[O:18][C:17](=[O:19])[CH2:16][C:15](=[O:20])[CH2:14]2)[CH:5]=1

Participants

4

Reactant 3

HCID 6344Dichloromethane2×HCID 516892Sodium BicarbonateHCID 167287006-Cyclopentyl-6-[2-(2,4-dimethoxyphenyl)ethyl]tetrahydropyran-2,4-dione

Product 1

HCID 167287016-[2-(5-Chloro-2,4-dimethoxy-phenyl)ethyl]-6-cyclopentyl-tetrahydropyran-2,4-dioneYield 44%

Conditions

Temperature
-5 °C

Procedure

A solution of 6-[2-(2,4-dimethoxyphenyl)ethyl]-6-cyclopentyldihydro-2H-pyran-2,4(3H)-dione (from example A(39); 4.50 g, 13 mmol) in CH2Cl2 (20 mL) was cooled to −5° C. and treated with a solution of SO2Cl2 (1.94 g, 14.3 mmol) in CH2Cl2 (10 mL) dropwise under nitrogen. The reaction mixture was stirred for an additional 15 minutes at −5° C., then allowed to warm gradually to room temperature. After a total reaction time of 2 h, an aqueous solution of NaHCO3 (5 wt %) was added to achieve a pH of 8 in the aqueous phase. The volatiles were removed in vacuo. The residue was treated with water and extracted with ethyl acetate (3×25 mL). The combined ethyl acetate extract was acidified to a pH 2 using 2 N HCl, then washed with water. The organic phase was dried over Na2SO4, filtered, and concentrated to a yellowish solid. Recrystallization from ether afforded the title product as a white solid (2.18 g, 44%).

Workup

  1. customwas cooled to −5° C.
  2. temperatureto warm gradually to room temperature
  3. customThe volatiles were removed in vacuo
  4. additionThe residue was treated with water
  5. extractionextracted with ethyl acetate (3×25 mL)
  6. extractionThe combined ethyl acetate extract
  7. washwashed with water
  8. dry with materialThe organic phase was dried over Na2SO4
  9. filtrationfiltered
  10. concentrationconcentrated to a yellowish solid
  11. customRecrystallization from ether

Sources & evidence

ORD record
ord-ea4449241156407997a725931dc3c283
Source dataset
uspto-grants-2006_12
Patent number
US07148226B2

Reaction notes

Loading…