Hydrochloric Acid → Methyl 2-((1R,2R,3aS,9aS)-2,3,3a,4,9,9a-hexahydro-2-(tert-butyldimethylsilyoxy)-1-((S,E)-3-hydroxyoct-1-enyl)-1H-cyclopenta[b]naphthalen-5-yloxy)acetate

HRID 245600Notes

Reaction equation

HRID 245600 reaction equation
[Si:1]([O:8][C@H:9]1[C@H:22](/[CH:23]=[CH:24]/[C@@H:25]([O:31][Si](C(C)(C)C)(C)C)[CH2:26][CH2:27][CH2:28][CH2:29][CH3:30])[C@H:12]2[CH2:13][C:14]3[CH:15]=[CH:16][CH:17]=[C:18]([OH:21])[C:19]=3[CH2:20][C@H:11]2[CH2:10]1)([C:4]([CH3:7])([CH3:6])[CH3:5])([CH3:3])[CH3:2].[OH-].[Na+].Cl.[C:42]([O:45][CH2:46]C)(=[O:44])[CH3:43]>BrCC(OC)=O>[Si:1]([O:8][C@H:9]1[C@H:22](/[CH:23]=[CH:24]/[C@@H:25]([OH:31])[CH2:26][CH2:27][CH2:28][CH2:29][CH3:30])[C@H:12]2[CH2:13][C:14]3[C:19]([CH2:20][C@H:11]2[CH2:10]1)=[C:18]([O:21][CH2:43][C:42]([O:45][CH3:46])=[O:44])[CH:17]=[CH:16][CH:15]=3)([C:4]([CH3:7])([CH3:6])[CH3:5])([CH3:3])[CH3:2]

Participants

6

Reactant 4

HCID 313Hydrochloric AcidHCID 8857Ethyl AcetateHCID 14798Sodium HydroxideHCID 86677387HCID 86677387, compound

Product 1

HCID 86703445Methyl 2-((1R,2R,3aS,9aS)-2,3,3a,4,9,9a-hexahydro-2-(tert-butyldimethylsilyoxy)-1-((S,E)-3-hydroxyoct-1-enyl)-1H-cyclopenta[b]naphthalen-5-yloxy)acetateYield 58%

Reagents, catalysts & solvents 1

HCID 60984Methyl bromoacetateSolvent

Procedure

(1R,2R,3aS,9aS)-2,3,3a,4,9,9a-hexahydro-2-(tert-butyldimethylsilyoxy)-1-((S,E)-3-(tert-butyldimethylsilyoxy)oct-1-enyl)-1H-cyclopenta[b]naphthalen-5-ol (0.5 g, 0.89 mmol) in methyl bromoacetate (3 ml) was treated with 50% NaOH (1 g). The mixture was stirred at room temperature for 60 min. The reaction mixture was cooled to 10° C. and 3N HCl was added slowly until pH=7, and then the reaction was exacted with ethyl acetate. The organic layers were combined and dried over anhydrous magnesium sulfate. The solid was filtered off. The solvent was evaporated off under vacuum. The crude product was purified by chromatography on silica gel using a mixture of hexane and ethyl acetate as a gradient eluent. 0.2 g of Methyl 2-((1R,2R,3aS,9aS)-2,3,3a,4,9,9a-hexahydro-2-(tert-butyldimethylsilyoxy)-1-((S,E)-3-hydroxyoct-1-enyl)-1H-cyclopenta[b]naphthalen-5-yloxy)acetate was obtained. The product was then dissolved in THF (1.3 ml), acetic acid (3.9 ml) and distilled water (1.3 ml) for overnight at room temperature. The reaction mixture was poured to saturated sodium bicarbonate aqueous (1.0 ml) and stirred for 30 minutes. The reaction mixture was phase separated and the aqueous layer was extracted with 20 ml ethyl acetate. The organic layers were combined and dried over anhydrous magnesium sulfate. The solid was filtered off. The solvent was evaporated off under vacuum. The crude product was purified by chromatography on silica gel using a mixture of hexane and ethyl acetate as a gradient eluent. The titled compound was obtained in a crystalline form. (Yield: 58%)

Workup

  1. temperatureThe reaction mixture was cooled to 10° C.
  2. dry with materialdried over anhydrous magnesium sulfate
  3. filtrationThe solid was filtered off
  4. customThe solvent was evaporated off under vacuum
  5. customThe crude product was purified by chromatography on silica gel using
  6. additiona mixture of hexane and ethyl acetate as a gradient eluent

Sources & evidence

ORD record
ord-0c9e20cf26ca409c865d5db67fc0e97f
Source dataset
uspto-grants-2014_02
Patent number
US08658837B2

Reaction notes

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