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

HRID 859708Notes

Reaction equation

HRID 859708 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) δ1.74 (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-77c7eb887d404b238877b381fdef4956
Source dataset
uspto-grants-2006_12
Patent number
US07151105B2

Reaction notes

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