p-Toluenesulfonic acid → (4R)-Tetrahydro-4α-hydroxy-6α-[(E)-4,4-bis(4-fluorophenyl)-3-(1-methyl-1H-tetrazol-5-yl)-1,3-butadienyl]-2H-pyran-2-one

HRID 330696Notes

Reaction equation

HRID 330696 reaction equation
[F:1][C:2]1[CH:7]=[CH:6][C:5]([C:8]([C:30]2[CH:35]=[CH:34][C:33]([F:36])=[CH:32][CH:31]=2)=[C:9]([C:24]2[N:28]([CH3:29])[N:27]=[N:26][N:25]=2)/[CH:10]=[CH:11]\[C@H:12]2[O:17]C(C)(C)[O:15][C@@H:14]([CH2:20][C:21](O)=[O:22])[CH2:13]2)=[CH:4][CH:3]=1.CC1C=CC(S(O)(=O)=O)=CC=1>C1COCC1.Cl>[F:36][C:33]1[CH:34]=[CH:35][C:30]([C:8]([C:5]2[CH:6]=[CH:7][C:2]([F:1])=[CH:3][CH:4]=2)=[C:9]([C:24]2[N:28]([CH3:29])[N:27]=[N:26][N:25]=2)/[CH:10]=[CH:11]/[C@H:12]2[O:17][C:21](=[O:22])[CH2:20][C@H:14]([OH:15])[CH2:13]2)=[CH:31][CH:32]=1

Participants

5

Reactant 2

HCID 6101p-Toluenesulfonic acidHCID 14423963HCID 14423963, compound

Product 1

HCID 9932838(4R)-Tetrahydro-4α-hydroxy-6α-[(E)-4,4-bis(4-fluorophenyl)-3-(1-methyl-1H-tetrazol-5-yl)-1,3-butadienyl]-2H-pyran-2-oneYield 40.7%

Reagents, catalysts & solvents 2

HCID 313Hydrochloric AcidSolventHCID 8028TetrahydrofuranSolvent

Procedure

Cis-(4R,6S)-6-[4,4-bis(4-fluorophenyl)-3-(1-methyl-1H-tetrazol-5-yl)-1,3-butadienyl]-2,2-dimethyl-1,3-dioxane-4-acetic acid (3.7 g, 7.45 mmol) was dissolved in a solution of THF (90 mL) and 0.2N HCl (60 mL) and allowed to stand for 16 hours. The solution was partitioned between ethyl acetate and water. The organic layer was washed with brine (2x), dried (Na2SO4), and concentrated under reduced pressure. The residue was dissolved in dry methylene chloride (60 mL) and stirred for 4 hours in the presence of 1-cyclohexyl-3-(2-morpholinomethyl) carbodiimide metho-p-toluenesulfonate (6.6 g, 15.6 mmol). The solution was concentrated under reduced pressure and the residue was partitioned between ethyl acetate and water. The organic layer was dried (Na2SO4) and concentrated under reduced pressure. The residue was purified by chromatography on silica gel (1:1/ethyl acetate:diethyl ether). After recrystallization from ethyl acetate-hexane, 1.33 g (40.1%) of the title compound was obtained as a white solid; m.p.=172°-173° C. [α]D25 =+237.8° (c=2.17, CHCl3).

Workup

  1. customThe solution was partitioned between ethyl acetate and water
  2. washThe organic layer was washed with brine (2x)
  3. dry with materialdried (Na2SO4)
  4. concentrationconcentrated under reduced pressure
  5. dissolutionThe residue was dissolved in dry methylene chloride (60 mL)
  6. concentrationThe solution was concentrated under reduced pressure
  7. customthe residue was partitioned between ethyl acetate and water
  8. dry with materialThe organic layer was dried (Na2SO4)
  9. concentrationconcentrated under reduced pressure
  10. customThe residue was purified by chromatography on silica gel (1:1/ethyl acetate:diethyl ether)
  11. customAfter recrystallization from ethyl acetate-hexane

Sources & evidence

ORD record
ord-23f06bee4a4b45eb9e1c22c4f1820fee
Source dataset
uspto-grants-1990_01
Patent number
US04897490

Reaction notes

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