Benzoyl chloride → (1R,2R,3aS,9aS)-2,3,3a,4,9,9a-hexahydro-2-(tert-butyldimethylsilyoxy)-1-((S,E)-3-(tert-butyl dimethylsilyoxy)oct-1-enyl)-1H-cyclopenta[b]naphthalen-5-yl benzoate

HRID 245598Notes

Reaction equation

HRID 245598 reaction equation
[C:1]([Si:5]([CH3:38])([CH3:37])[O:6][C@H:7]1[C@H:20](/[CH:21]=[CH:22]/[C@@H:23]([O:29][Si:30]([C:33]([CH3:36])([CH3:35])[CH3:34])([CH3:32])[CH3:31])[CH2:24][CH2:25][CH2:26][CH2:27][CH3:28])[C@H:10]2[CH2:11][C:12]3[CH:13]=[CH:14][CH:15]=[C:16]([OH:19])[C:17]=3[CH2:18][C@H:9]2[CH2:8]1)([CH3:4])([CH3:3])[CH3:2].[H-].[Na+].[C:41](Cl)(=[O:48])[C:42]1[CH:47]=[CH:46][CH:45]=[CH:44][CH:43]=1>O1CCCC1>[C:41]([O:19][C:16]1[CH:15]=[CH:14][CH:13]=[C:12]2[C:17]=1[CH2:18][C@H:9]1[CH2:8][C@@H:7]([O:6][Si:5]([C:1]([CH3:3])([CH3:4])[CH3:2])([CH3:37])[CH3:38])[C@H:20](/[CH:21]=[CH:22]/[C@@H:23]([O:29][Si:30]([C:33]([CH3:36])([CH3:35])[CH3:34])([CH3:32])[CH3:31])[CH2:24][CH2:25][CH2:26][CH2:27][CH3:28])[C@H:10]1[CH2:11]2)(=[O:48])[C:42]1[CH:47]=[CH:46][CH:45]=[CH:44][CH:43]=1

Participants

5

Reactant 3

HCID 7412Benzoyl chlorideHCID 24758Sodium hydrideHCID 86677387HCID 86677387, compound

Product 1

HCID 86677386(1R,2R,3aS,9aS)-2,3,3a,4,9,9a-hexahydro-2-(tert-butyldimethylsilyoxy)-1-((S,E)-3-(tert-butyl dimethylsilyoxy)oct-1-enyl)-1H-cyclopenta[b]naphthalen-5-yl benzoateYield 88.5%

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent

Procedure

2 g (3.58 mmole, from Example 18) of (1R,2R,3aS,9aS)-2,3,3a,4,9,9a-hexahydro-2-(tert-butyldimethyl-silyoxy)-1-((S,E)-3-(tert-butyldimethylsilyoxy)oct-1-enyl)-1H-cyclopenta[b]naphthalen-5-ol, which contains 6% para-cyclized isomer, in dry tetrahydrofuran (20 ml) was treated with sodium hydride (0.29 g, 7.16 mol) at 0° C. and stirred for 10 minutes at room temperature, followed by dropwise addition of benzoyl chloride (0.63 ml, 5.37 mmol). After 30 minutes, the reaction was cooled to 10° C., diluted with ice cold brine (10 ml) and extracted with ethyl acetate (10 ml). The reaction mixture was phase separated and the aqueous layer was extracted 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. 2.1 g of (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-yl benzoate was obtained. The product was then dissolved in tetrahydrofuran (4.2 ml), and treated with acetic acid (12.6 ml) and distilled water (4.2 ml) overnight at room temperature. The reaction then was diluted with saturated sodium bicarbonate aqueous (50 ml) and extracted with ethyl acetate (60 ml). The reaction mixture was phase separated and the aqueous layer was extracted 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. The product was obtained in a crystalline form. MP: 140˜141° C. Yield: 68%.

Workup

  1. waitAfter 30 minutes
  2. temperaturethe reaction was cooled to 10° C.
  3. extractionextracted with ethyl acetate (10 ml)
  4. customseparated
  5. extractionthe aqueous layer was extracted with ethyl acetate
  6. dry with materialdried over anhydrous magnesium sulfate
  7. filtrationThe solid was filtered off
  8. customThe solvent was evaporated off under vacuum
  9. customThe crude product was purified by chromatography on silica gel using
  10. additiona mixture of hexane and ethyl acetate as a gradient eluent

Sources & evidence

ORD record
ord-6d194e6864364ac1a427710ac981987e
Source dataset
uspto-grants-2014_02
Patent number
US08658837B2

Reaction notes

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