p-Toluenesulfonic acid monohydrate → HCID 70805938, compound

HRID 517394Notes

Reaction equation

HRID 517394 reaction equation
O.C1(C)C=CC(S(O)(=O)=O)=CC=1.[F:13][C:14]([F:46])([CH2:38][O:39][C:40]1[CH:45]=[CH:44][CH:43]=[CH:42][CH:41]=1)/[CH:15]=[CH:16]/[C@@H:17]1[C@@H:29]2[C@@H:20]([O:21][C:22](=[O:30])[CH2:23][CH2:24][CH2:25][CH:26]=[CH:27][CH2:28]2)[CH2:19][C@H:18]1[O:31]C1CCCCO1>CO>[F:46][C:14]([F:13])([CH2:38][O:39][C:40]1[CH:45]=[CH:44][CH:43]=[CH:42][CH:41]=1)/[CH:15]=[CH:16]/[C@@H:17]1[C@@H:29]2[C@@H:20]([O:21][C:22](=[O:30])[CH2:23][CH2:24][CH2:25][CH:26]=[CH:27][CH2:28]2)[CH2:19][C@H:18]1[OH:31]

Participants

4

Reactant 2

HCID 521998p-Toluenesulfonic acid monohydrateHCID 117873614HCID 117873614, compound

Product 1

HCID 70805938HCID 70805938, compoundYield 93.4%

Reagents, catalysts & solvents 1

HCID 887MethanolSolvent

Procedure

p-toluenesulfonic acid monohydrate (10.37 g, 54.5 mmol) was add to a stirred solution of (8aR,9R,10R,11aS,Z)-9-((E)-3,3-difluoro-4-phenoxybut-1-en-1-yl)-10-((tetrahydro-2H-pyran-2-yl)oxy)-4,5,8,8a,9,10,11,11a-octahydrocyclopenta[b]oxecin-2(3H)-one (26.0 g from example 33) in methanol (200 mL). The mixture was stirred for 2 hr at room temperature (TLC monitoring). Then, the reaction mixture was quenched with saturated sodium bicarbonate aqueous solution (300 mL), and the methanol was removed under reduced pressure. The residue was extracted with ethyl acetate (200 mL). The organic layer was separated. The aqueous layer was extracted with ethyl acetate (200 mL). The combined organic layers were dried over magnesium sulfate, filtered and concentrated under reduced pressure to give 30.0 g of crude product. The crude product was purified by column chromatography providing 20.0 g of the titled compound (90.0% yield).

Workup

  1. customThen, the reaction mixture was quenched with saturated sodium bicarbonate aqueous solution (300 mL)
  2. customthe methanol was removed under reduced pressure
  3. extractionThe residue was extracted with ethyl acetate (200 mL)
  4. customThe organic layer was separated
  5. extractionThe aqueous layer was extracted with ethyl acetate (200 mL)
  6. dry with materialThe combined organic layers were dried over magnesium sulfate
  7. filtrationfiltered
  8. concentrationconcentrated under reduced pressure
  9. customto give 30.0 g of crude product
  10. customThe crude product was purified by column chromatography

Sources & evidence

ORD record
ord-9b52ef78adba4be2b843f02b33942474
Source dataset
uspto-grants-2015_08
Patent number
US09115109B2

Reaction notes

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