Methanol → ((3aR,4R,5R,6aS)-4-((E,3S)-3-hydroxy-5-phenylpent-1-enyl)-2-oxo-3,3a,4,5,6,6a-hexahydrocyclopenta(b)furan-5-yl) benzoate

HRID 449168Notes

Reaction equation

HRID 449168 reaction equation
[O:1]=[C:2]1[O:6][C@H:5]2[CH2:7][C@@H:8]([O:22][C:23](=[O:30])[C:24]3[CH:29]=[CH:28][CH:27]=[CH:26][CH:25]=3)[C@H:9](/[CH:10]=[CH:11]/[C:12](=[O:21])[CH2:13][CH2:14][C:15]3[CH:20]=[CH:19][CH:18]=[CH:17][CH:16]=3)[C@H:4]2[CH2:3]1.CO>C1COCC1>[OH:21][C@@H:12]([CH2:13][CH2:14][C:15]1[CH:20]=[CH:19][CH:18]=[CH:17][CH:16]=1)/[CH:11]=[CH:10]/[C@@H:9]1[C@@H:4]2[C@@H:5]([O:6][C:2](=[O:1])[CH2:3]2)[CH2:7][C@H:8]1[O:22][C:23](=[O:30])[C:24]1[CH:25]=[CH:26][CH:27]=[CH:28][CH:29]=1

Participants

4

Reactant 2

HCID 887MethanolHCID 22821307HCID 22821307, compound

Product 1

HCID 10201368((3aR,4R,5R,6aS)-4-((E,3S)-3-hydroxy-5-phenylpent-1-enyl)-2-oxo-3,3a,4,5,6,6a-hexahydrocyclopenta(b)furan-5-yl) benzoateYield 81.6%

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent

Procedure

To a solution of 50 g of compound 20a (MW=406.8; 1.0 eq.; prepared as described in example 2) in 500 mL of dry THF was slowly added 190 mL of (−)-DIP-Cl solution (MW=320.76; 2.75 eq. 63% in heptane) at −30° C. After stirring for 6 h 180 mL of methanol were added and the mixture was warmed to room temperature. After removal of the solvent under reduced pressure, the residue was dissolved in methanol/water (10/1) and extracted twice with heptane. After concentration of the aqueous layer, ethyl acetate was added and the resulting mixture was consecutively extracted with an aqueous NaCl solution (9%) and with an aqueous NaHCO3 solution (8.6%). The organic solvents were removed under reduced pressure and the residue was recrystallized from ethyl acetate/n-heptane (1/7) to give 41 g of the title compound after drying (40° C., 10 mbar; yield=81.2%, de(S)=89.2%).

Workup

  1. customat −30° C
  2. additionwere added
  3. customAfter removal of the solvent under reduced pressure
  4. dissolutionthe residue was dissolved in methanol/water (10/1)
  5. extractionextracted twice with heptane
  6. additionAfter concentration of the aqueous layer, ethyl acetate was added
  7. extractionthe resulting mixture was consecutively extracted with an aqueous NaCl solution (9%) and with an aqueous NaHCO3 solution (8.6%)
  8. customThe organic solvents were removed under reduced pressure
  9. customthe residue was recrystallized from ethyl acetate/n-heptane (1/7)

Sources & evidence

ORD record
ord-c9b87f347ff3445ea9b03e45622ddde3
Source dataset
uspto-grants-2013_07
Patent number
US08481758B2

Reaction notes

Loading…