Tetrabutylammonium Fluoride → Travoprost Impurity 26

HRID 517383Notes

Reaction equation

HRID 517383 reaction equation
[Si]([O:8][C@@H:9]1[CH2:22][C@@H:12]2[O:13][C:14](=[O:21])[CH2:15][CH2:16][CH2:17][CH:18]=[CH:19][CH2:20][C@@H:11]2[C@H:10]1/[CH:23]=[CH:24]/[C@@H:25]([O:38][Si](CC)(CC)CC)[CH2:26][O:27][C:28]1[CH:33]=[CH:32][CH:31]=[C:30]([C:34]([F:37])([F:36])[F:35])[CH:29]=1)(C(C)(C)C)(C)C.CCCC[N+](CCCC)(CCCC)CCCC.[F-]>>[OH:8][C@@H:9]1[CH2:22][C@@H:12]2[O:13][C:14](=[O:21])[CH2:15][CH2:16][CH2:17][CH:18]=[CH:19][CH2:20][C@@H:11]2[C@H:10]1/[CH:23]=[CH:24]/[C@@H:25]([OH:38])[CH2:26][O:27][C:28]1[CH:33]=[CH:32][CH:31]=[C:30]([C:34]([F:37])([F:35])[F:36])[CH:29]=1

Participants

3

Reactant 2

HCID 2724141Tetrabutylammonium FluorideHCID 131733347(8aR,9R,10R,11 aS,Z)-10-(tert-butyldimethylsilyloxy)-9-((R,E)-3-(triethylsilyloxy)-4-(3-(trifluoromethyl)phenoxy)but-1-enyl)-4,5,8,8a,9,10,11,11a-octahydrocyclopenta[b]oxecin-2(3H)-one

Product 1

HCID 68031942Travoprost Impurity 26Yield 756.8%

Procedure

(8aR,9R,10R,11 aS,Z)-10-(tert-butyldimethylsilyloxy)-9-((R,E)-3-(triethylsilyloxy)-4-(3-(trifluoromethyl)phenoxy)but-1-enyl)-4,5,8,8a,9,10,11,11a-octahydrocyclopenta[b]oxecin-2(3H)-one (20 mg, 0.003 mmol) and 1 ml TBAF (1M in tetrahydrofuran) was added into 10 ml round-bottom flask. The reaction mixture was stirred for 2 hours and quenched by 1 ml saturated NaHCO3 aqueous solution. Then, the mixture was phase separated and the aqueous layer was extracted with ethyl acetate. The organic layers were combined and dried over anhydrous MgSO4. The solid was filtered off and organic solvent was evaporated off under vacuum. The crude product was purified by chromatography and then concentrated under reduced pressure to provide 10 mg of the title compound as an oil. (80% yield).

Workup

  1. customquenched by 1 ml saturated NaHCO3 aqueous solution
  2. customseparated
  3. extractionthe aqueous layer was extracted with ethyl acetate
  4. dry with materialdried over anhydrous MgSO4
  5. filtrationThe solid was filtered off
  6. customorganic solvent was evaporated off under vacuum
  7. customThe crude product was purified by chromatography
  8. concentrationconcentrated under reduced pressure

Sources & evidence

ORD record
ord-11c2e127410e4da3b7d5129e39e85aec
Source dataset
uspto-grants-2015_08
Patent number
US09115109B2

Reaction notes

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