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

HRID 2387098Notes

Reaction equation

HRID 2387098 reaction equation
[CH:1]1([C:6]2([CH2:14][CH2:15][C:16]3[CH:21]=[CH:20][C:19]([O:22][CH3:23])=[CH:18][C:17]=3[O:24][CH3:25])[O:11][C:10](=[O:12])[CH2:9][C:8](=[O:13])[CH2:7]2)[CH2:5][CH2:4][CH2:3][CH2:2]1.C([O-])(O)=O.[Na+].C(Cl)[Cl:32]>>[Cl:32][C:20]1[C:19]([O:22][CH3:23])=[CH:18][C:17]([O:24][CH3:25])=[C:16]([CH2:15][CH2:14][C:6]2([CH:1]3[CH2:5][CH2:4][CH2:3][CH2:2]3)[O:11][C:10](=[O:12])[CH2:9][C:8](=[O:13])[CH2:7]2)[CH:21]=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 Step 5, above) (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%). 1H NMR (CDCl3) δ 1.74 (m, 8H), 2.32 (m, 1H), 2.58 (m, 2H), 2.78 (s, 2H), 3.43 (s, 2H), 3.82 (s, 3H), 3.92 (s, 3H), 6.44 (s, 1H), 7.07 (s, 1H). HRMS calcd for C20H25O5Cl (M+H+): 381.1469, found 381.1475.

Workup

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

Sources & evidence

ORD record
ord-29a63251de0247958d14caf5695c8c54
Source dataset
uspto-grants-2012_09
Patent number
US08268835B2

Reaction notes

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