p-Toluenesulfonic acid monohydrate → Travoprost

HRID 517375

Reaction equation

HRID 517375 reaction equation
C([Si](CC)(CC)[O:4][C@@H:5]1[CH2:9][C@H:8]([O:10][Si](CC)(CC)CC)[C@H:7]([CH2:18]/[CH:19]=[CH:20]\[CH2:21][CH2:22][CH2:23][C:24]([O:26][CH:27]([CH3:29])[CH3:28])=[O:25])[C@H:6]1/[CH:30]=[CH:31]/[C@@H:32]([O:45][Si](CC)(CC)CC)[CH2:33][O:34][C:35]1[CH:40]=[CH:39][CH:38]=[C:37]([C:41]([F:44])([F:43])[F:42])[CH:36]=1)C.O.C1(C)C=CC(S(O)(=O)=O)=CC=1>CC(C)=O.O>[OH:4][C@@H:5]1[CH2:9][C@H:8]([OH:10])[C@H:7]([CH2:18]/[CH:19]=[CH:20]\[CH2:21][CH2:22][CH2:23][C:24]([O:26][CH:27]([CH3:29])[CH3:28])=[O:25])[C@H:6]1/[CH:30]=[CH:31]/[C@@H:32]([OH:45])[CH2:33][O:34][C:35]1[CH:40]=[CH:39][CH:38]=[C:37]([C:41]([F:42])([F:43])[F:44])[CH:36]=1

Participants

5

Reactant 2

HCID 521998p-Toluenesulfonic acid monohydrateHCID 131733340(Z)-isopropyl 7-((1R,2R,3R,5S)-3,5-bis((triethylsilyl)oxy)-2-((R,E)-3-((triethylsilyl)oxy)-4-(3-(trifluoromethyl)phenoxy)but-1-en-1-yl)cyclopentyl)hept-5-enoate

Product 1

HCID 5282226TravoprostYield 92.7%

Reagents, catalysts & solvents 2

HCID 180AcetoneSolventHCID 962WaterSolvent

Procedure

The product of Example 11 (0.8 g) was dissolved in 10 ml acetone and 2 ml water, followed by addition of 0.1 g p-toluenesulfonic acid monohydrate. The reaction solution was stirred at room temperature for 1 hour and concentrated until two separate layers were observed. 30 ml ethyl acetate was added for extraction and phase separation. The organic layer was washed with saturated sodium bicarbonate solution and brine, dried over anhydrous magnesium sulfate, and subjected to vacuum evaporation for removal of the solvent until dryness. The crude Travoprost was purified by column chromatography and then concentrated under reduced pressure to provide 0.44 g of Travoprost. UPLC (ACQUITY UPLC HSS C18) analysis of the product showed that no isomer and impurities were detectable and the purity was higher then 99.9%.

Workup

  1. concentrationconcentrated until two
  2. customseparate layers
  3. addition30 ml ethyl acetate was added for extraction and phase separation
  4. washThe organic layer was washed with saturated sodium bicarbonate solution and brine
  5. dry with materialdried over anhydrous magnesium sulfate
  6. customsubjected to vacuum evaporation for removal of the solvent until dryness
  7. customThe crude Travoprost was purified by column chromatography
  8. concentrationconcentrated under reduced pressure

Sources & evidence

ORD record
ord-4679549259c54a2a943f38a28c952546
Source dataset
uspto-grants-2015_08
Patent number
US09115109B2

Linked notes

Loading…