1,2-Dichloroethane → 4-(4-chlorophenyl)-2-pyridin-4-yl-5,6,7,8-tetrahydro-4H-cyclohepta[b]thiophene-5-ol

HRID 1615525Notes

Reaction equation

HRID 1615525 reaction equation
[Cl:1][C:2]1[CH:7]=[CH:6][C:5]([C:8]2(O)[C:14]3[CH:15]=[C:16]([C:18]4[CH:23]=[CH:22][N:21]=[CH:20][CH:19]=4)[S:17][C:13]=3[CH2:12][CH2:11][CH2:10][CH:9]2[OH:24])=[CH:4][CH:3]=1.ClCCCl.C([SiH](CC)CC)C.FC(F)(F)S(O)(=O)=O.C([O-])(O)=O.[Na+]>>[Cl:1][C:2]1[CH:7]=[CH:6][C:5]([CH:8]2[C:14]3[CH:15]=[C:16]([C:18]4[CH:19]=[CH:20][N:21]=[CH:22][CH:23]=4)[S:17][C:13]=3[CH2:12][CH2:11][CH2:10][CH:9]2[OH:24])=[CH:4][CH:3]=1

Participants

6

Reactant 5

HCID 111,2-DichloroethaneHCID 12052TriethylsilaneHCID 62406Trifluoromethanesulfonic acidHCID 516892Sodium BicarbonateHCID 681829224-(4-chlorophenyl)-2-pyridin-4-yl-5,6,7,8-tetrahydro-4H-cyclohepta thiophene-4,5-diol

Product 1

HCID 681830874-(4-chlorophenyl)-2-pyridin-4-yl-5,6,7,8-tetrahydro-4H-cyclohepta[b]thiophene-5-olYield 77%

Conditions

Temperature
50 °C

Procedure

To a solution of 4-(4-chlorophenyl)-2-pyridin-4-yl-5,6,7,8-tetrahydro-4H-cyclohepta thiophene-4,5-diol (197.5 mg, 0.531 mmol) in 1,2-dichloroethane (2.9 mL, 37 mmol) were added triethylsilane (0.848 mL, 5.31 mmol) and trifluoromethanesulfonic acid (47.00 uL, 0.531 mmol). The resulting reddish solution was heated at 50° C. for 16 hr. Then the reaction mixture was allowed to cool to rt, and neutralized to pH 7 by the addition of saturated NaHCO3. The organic layer was separated and the aqueous phase was extracted with ethyl acetate (3×10 mL). The combined organic phases were washed with brine (10 mL) then dried over anhydrous MgSO4. Insoluble materials were removed by filtration and then the filtrate was concentrated and the obtained residue was purified by column chromatography (SiO2, elution with 0-100% EA/hexane) to give the title compound as a yellow solid (145.6 mg, 77% yield). LCMS: (AA) ES+ , 356/358. 1H NMR (300 MHz, DMSO) δ, 8.48 (dd, J=4.5, 1.6 Hz, 2H), 7.45 (td, 4.4, 1.7 Hz, 2H), 7.42-7.20 (m, 4H), 5.75 (d, J=1.8 Hz, 1H), 5.03 (d, J=3.6 Hz, 1H), 4.45 (d, J=2.5 Hz, 1H), 4.01 (s, 1H), 3.05-2.61 (m, 2H), 2.02-1.43 (m, 4H).

Workup

  1. temperatureto cool to rt
  2. customThe organic layer was separated
  3. extractionthe aqueous phase was extracted with ethyl acetate (3×10 mL)
  4. washThe combined organic phases were washed with brine (10 mL)
  5. dry with materialthen dried over anhydrous MgSO4
  6. customInsoluble materials were removed by filtration
  7. concentrationthe filtrate was concentrated
  8. customthe obtained residue was purified by column chromatography (SiO2, elution with 0-100% EA/hexane)

Sources & evidence

ORD record
ord-aed3dbaa27264f8c95ba99b3f5c65459
Source dataset
uspto-grants-2014_07
Patent number
US08765746B2

Reaction notes

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