Hydrochloric Acid → Bimatoprost Acid

HRID 517407Notes

Reaction equation

HRID 517407 reaction equation
[OH:1][C@@H:2]1[CH2:15][C@@H:5]2[O:6][C:7](=[O:14])[CH2:8][CH2:9][CH2:10][CH:11]=[CH:12][CH2:13][C@@H:4]2[C@H:3]1/[CH:16]=[CH:17]/[C@@H:18]([OH:27])[CH2:19][CH2:20][C:21]1[CH:26]=[CH:25][CH:24]=[CH:23][CH:22]=1.Cl.CC([OH:32])C>[OH-].[K+].C([O-])(O)=O.[Na+]>[OH:1][C@@H:2]1[CH2:15][C@H:5]([OH:32])[C@H:4]([CH2:13]/[CH:12]=[CH:11]\[CH2:10][CH2:9][CH2:8][C:7]([OH:6])=[O:14])[C@H:3]1/[CH:16]=[CH:17]/[C@@H:18]([OH:27])[CH2:19][CH2:20][C:21]1[CH:26]=[CH:25][CH:24]=[CH:23][CH:22]=1

Participants

6

Reactant 3

HCID 313Hydrochloric AcidHCID 3776IsopropanolHCID 49872499(6Z,8aR,9R,10R,11aS)-4,5,8,8a,9,10,11, 11a-octahydro-10-hydroxy-9-((S,E)-3-hydroxy-5-phenylpent-1-enyl)cyclopenta[b]oxecin-2(3H)-one

Product 1

HCID 5283081Bimatoprost Acid

Reagents, catalysts & solvents 2

HCID 14797Potassium HydroxideSolventHCID 516892Sodium BicarbonateSolvent

Procedure

A solution of (6Z,8aR,9R,10R,11aS)-4,5,8,8a,9,10,11,11a-octahydro-10-hydroxy-9-((S,E)-3-hydroxy-5-phenylpent-1-enyl)cyclopenta[b]oxecin-2(3H)-one (2 g, 5.4 mmol) in 20 ml 2-propanol and 6.3 ml of 3 N potassium hydroxide aqueous solution in 50 mL round-bottom flask was refluxed and stirred for 2 hours. The mixture was cooled to room temperature and adjusted to a pH of 8.5 with 3 N hydrochloric acid aqueous solution. Subsequently, the 2-propanol was removed under reduced pressure and resulting mixture was diluted with 30 ml saturated NaHCO3 aqueous solution. The basic aqueous solution was extracted with 30 ml ethyl acetate twice and the aqueous layer was adjusted to a pH of 3 with 3 N hydrochloric acid aqueous solution. Then, the acidic aqueous layer was extracted with 50 ml ethyl acetate. The organic layer was dried over anhydrous MgSO4, the solid was filtered off and organic solvent was evaporated off under vacuum to obtain 2 g of the crude title compound.

Workup

  1. customSubsequently, the 2-propanol was removed under reduced pressure
  2. customresulting mixture
  3. extractionThe basic aqueous solution was extracted with 30 ml ethyl acetate twice
  4. extractionThen, the acidic aqueous layer was extracted with 50 ml ethyl acetate
  5. dry with materialThe organic layer was dried over anhydrous MgSO4
  6. filtrationthe solid was filtered off
  7. customorganic solvent was evaporated off under vacuum

Sources & evidence

ORD record
ord-8c6f017696744e069a9cca20106b6b1f
Source dataset
uspto-grants-2015_08
Patent number
US09115109B2

Reaction notes

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