Citric Acid → Methyl (5Z)-(9R,11R,13RS,14RS,15S)-9-chloro-11,15-dihydroxy-16,16-dimethyl-13,14-epoxy-5-prostenoate

HRID 229943

Reaction equation

HRID 229943 reaction equation
[Cl:1][C@@H:2]1[CH2:16][C@@H:15]([OH:17])[C@H:14](/[CH:18]=[CH:19]/[C@@H:20]([OH:28])[C:21]([CH3:27])([CH3:26])[CH2:22][CH2:23][CH2:24][CH3:25])[C@H:3]1[CH2:4]/[CH:5]=[CH:6]\[CH2:7][CH2:8][CH2:9][C:10]([O:12][CH3:13])=[O:11].C([O:33]O)(C)(C)C.C(O)(=O)CC(CC(O)=O)(C(O)=O)O>C(Cl)Cl.O.CC(C)[O-].[Ti+4].CC(C)[O-].CC(C)[O-].CC(C)[O-].S([O-])([O-])(=O)=O.[Fe+2]>[Cl:1][C@@H:2]1[CH2:16][C@@H:15]([OH:17])[C@H:14]([CH:18]2[O:33][CH:19]2[C@@H:20]([OH:28])[C:21]([CH3:27])([CH3:26])[CH2:22][CH2:23][CH2:24][CH3:25])[C@H:3]1[CH2:4]/[CH:5]=[CH:6]\[CH2:7][CH2:8][CH2:9][C:10]([O:12][CH3:13])=[O:11]

Participants

8

Reactant 3

HCID 311Citric AcidHCID 6410tert-Butyl hydroperoxideHCID 13853250Methyl (5Z,13E,15R)-9beta-chloro-11alpha,15-dihydroxy-16,16-dimethylprosta-5,13-dien-1-oate

Product 1

HCID 57759195Methyl (5Z)-(9R,11R,13RS,14RS,15S)-9-chloro-11,15-dihydroxy-16,16-dimethyl-13,14-epoxy-5-prostenoate

Reagents, catalysts & solvents 4

HCID 11026Titanium isopropoxideCatalystHCID 24393Ferrous SulfateCatalystHCID 962WaterSolventHCID 6344DichloromethaneSolvent

Conditions

Temperature
-20 °C

Procedure

4.7 mL of titanium(IV) isopropoxide are added dropwise to a solution of 6.52 g of methyl (5Z,13E)-(9R,11R,15R)-9-chloro-11,15-dihydroxy-16,16-dimethyl-5,13-prostadienoate in 33 mL of methylene chloride at −20° C. under nitrogen, and the mixture is stirred at −20° C. for 30 min. Six mL of tert-butyl hydroperoxide are then added to the reaction mixture. A solution of 10 g of iron sulphate and 20 g of citric acid in 100 mL of water is subsequently added, and the mixture is extracted 3× with methylene chloride. The combined organic phases are washed 1× with saturated sodium chloride solution, dried over sodium sulphate and concentrated in vacuo. Chromatography on silica gel with methylene chloride/ethyl acetate (0-40%) results in 3.55 g of the epoxide as a colourless oil.

Workup

  1. extractionthe mixture is extracted 3× with methylene chloride
  2. washThe combined organic phases are washed 1× with saturated sodium chloride solution
  3. dry with materialdried over sodium sulphate
  4. concentrationconcentrated in vacuo
  5. customChromatography on silica gel with methylene chloride/ethyl acetate (0-40%) results in 3.55 g of the epoxide as a colourless oil

Sources & evidence

ORD record
ord-585aaab029684af5995ae20f693cc2a5
Source dataset
uspto-grants-2009_07
Patent number
US07563924B2

Linked notes

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