Dichloroacetic Acid → HCID 72545205, compound

HRID 1506849Notes

Reaction equation

HRID 1506849 reaction equation
[H-].[Na+].C1OCCOCCOCCOCCOCCOC1.Cl[CH:22](Cl)[C:23]([OH:25])=[O:24].[CH:27]1([C:33]([CH:47]2[CH2:52][CH2:51][CH2:50][CH2:49][CH2:48]2)([OH:46])[C:34]2[CH:39]=[CH:38][C:37]([N:40]3[CH:44]=[CH:43][CH:42]=[CH:41]3)=[CH:36][C:35]=2[OH:45])[CH2:32][CH2:31][CH2:30][CH2:29][CH2:28]1>O1CCOCC1>[CH:47]1([C:33]2([CH:27]3[CH2:28][CH2:29][CH2:30][CH2:31][CH2:32]3)[C:34]3[CH:39]=[CH:38][C:37]([N:40]4[CH:44]=[CH:43][CH:42]=[CH:41]4)=[CH:36][C:35]=3[O:45][CH:22]([C:23]([OH:25])=[O:24])[O:46]2)[CH2:52][CH2:51][CH2:50][CH2:49][CH2:48]1

Participants

6

Reactant 4

HCID 6597Dichloroacetic AcidHCID 24758Sodium hydrideHCID 2855718-Crown-6HCID 89906742HCID 89906742, compound

Product 1

HCID 72545205HCID 72545205, compound

Reagents, catalysts & solvents 1

HCID 312751,4-DioxaneSolvent3×

Conditions

Temperature
60 °C

Procedure

To a suspension of 228 mg of NaH (60% dispersion in mineral oil) and 18 mg of 18-crown-6 ether in 8 ml of anhydrous dioxane, a solution of 2.3 ml of a solution of dichloroacetic acid (1 M) in anhydrous dioxane was slowly added at room temperature. The reaction mixture was heated to 60° C. and a solution of 504 mg of 2-(Dicyclohexyl-hydroxy-methyl)-5-pyrrol-1-yl-phenol in 6 mL anhydrous dioxane was added and stirred at 95° C. for 6 h. After cooling to 0° C., the reaction mixture was quenched with 2 ml of isopropanol and poured on ice. The aqueous phase was extracted with ether, then acidified with HCl (2 M, to pH 1), and extracted with ethyl acetate. The combined organic layers were dried over MgSO4, filtered and concentrated under reduced pressure. The residue was purified by preparative HPLC (C18 reverse phase column, elution with a water/MeCN gradient with 0.1% TFA). The fractions containing the product were evaporated and lyophilized to yield a white solid. Yield: 118 mg.

Workup

  1. temperatureAfter cooling to 0° C.
  2. customthe reaction mixture was quenched with 2 ml of isopropanol
  3. additionpoured on ice
  4. extractionThe aqueous phase was extracted with ether
  5. extractionextracted with ethyl acetate
  6. dry with materialThe combined organic layers were dried over MgSO4
  7. filtrationfiltered
  8. concentrationconcentrated under reduced pressure
  9. customThe residue was purified by preparative HPLC (
  10. washC18 reverse phase column, elution with a water/MeCN gradient with 0.1% TFA)
  11. additionThe fractions containing the product
  12. customwere evaporated
  13. customto yield a white solid

Sources & evidence

ORD record
ord-c7716a59f7f743b79aed4456bec263a3
Source dataset
uspto-grants-2015_12
Patent number
US09221784B2

Reaction notes

Loading…