Acetone → 4-(4-chlorophenyl)-2-pyridin-4-yl-5,6,7,8-tetrahydro-4H-cyclohepta thiophene-4,5-diol

HRID 1615524Notes

Reaction equation

HRID 1615524 reaction equation
[Cl:1][C:2]1[CH:7]=[CH:6][C:5]([C:8]2[C:17]3[CH:16]=[C:15]([C:18]4[CH:23]=[CH:22][N:21]=[CH:20][CH:19]=4)[S:14][C:13]=3[CH2:12][CH2:11][CH2:10][CH:9]=2)=[CH:4][CH:3]=1.C([OH:28])(C)(C)C.CC(C)=O.C[N+]1([O-])CCOCC1.[OH2:41]>C(OCC)(=O)C.[Os](=O)(=O)(=O)=O>[Cl:1][C:2]1[CH:7]=[CH:6][C:5]([C:8]2([OH:28])[C:17]3[CH:16]=[C:15]([C:18]4[CH:19]=[CH:20][N:21]=[CH:22][CH:23]=4)[S:14][C:13]=3[CH2:12][CH2:11][CH2:10][CH:9]2[OH:41])=[CH:4][CH:3]=1

Participants

8

Reactant 5

HCID 180AcetoneHCID 962Water3×HCID 6386tert-ButanolHCID 82029Methyl morpholine oxideHCID 68183344HCID 68183344, compound

Product 1

HCID 681829224-(4-chlorophenyl)-2-pyridin-4-yl-5,6,7,8-tetrahydro-4H-cyclohepta thiophene-4,5-diolYield 72%

Reagents, catalysts & solvents 2

HCID 30318Osmium TetroxideCatalystHCID 8857Ethyl AcetateSolvent

Conditions

Temperature
50 °C

Procedure

To a solution of 4-[4-(4-chlorophenyl)-7,8-dihydro-6H-cyclohepta[b]thien-2-yl]pyridine (304.0 mg, 0.899 mmol) in tert-butyl alcohol (2.06 mL, 21.5 mmol) were added water (3.43 mL) and acetone (20.56 mL). N-methylmorpholine N-oxide (210.8 mg, 1.79 mmol) and 4% osmium tetroxide in water (0.164 mL, 0.0269 mmol) were added and the resulting pinkish suspension was heated at 50° C. for 3 hr. The reaction mixture was allowed to cool to rt and then diluted with ethyl acetate (15 mL) and water (10 mL), 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 0-20% MeOH/DCM) to give the title compound as a yellow foam (241.8 mg, 72% yield). LCMS: (FA) ES+ , 372/374. 1H NMR (400 MHz, DMSO) δ 8.50 (dd, J=4.6, 1.6 Hz, 2H), 7.49 (d, J=13.4 Hz, 1H), 7.44 (dd, J=4.6, 1.6 Hz, 2H), 7.38 (d, J=8.6 Hz, 2H), 7.25 (d, J=8.6 Hz, 2H), 5.75 (s, 1H), 5.71 (s, 1H), 4.83 (d, J=4.8 Hz, 1H), 4.14 (t, J=5.1 Hz, 1H), 2.93 (dd, J=15.7, 3.9 Hz, 1H), 2.75-2.55 (m, 1H), 2.05-1.73 (m, 2H), 1.52 (d, J=3.7 Hz, 1H), 1.38 (t, J=12.9 Hz, 1H).

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, Insoluble materials
  6. customwere removed by filtration
  7. concentrationthe filtrate was concentrated
  8. customthe obtained residue was purified by column chromatography (SiO2, elution with 0-20% MeOH/DCM)

Sources & evidence

ORD record
ord-aef50ac426464420ba1442aaec253ee8
Source dataset
uspto-grants-2014_07
Patent number
US08765746B2

Reaction notes

Loading…