Water → HCID 86669801, compound

HRID 1615577Notes

Reaction equation

HRID 1615577 reaction equation
[Cl:1][C:2]1[CH:7]=[CH:6][C:5]([CH:8]2[CH2:13][NH:12][C:11](=[O:14])[C:10]3[S:15][C:16]([N:20]4[CH2:25][CH2:24][O:23][CH2:22][CH2:21]4)=[C:17]([CH:18]=C)[C:9]2=3)=[CH:4][CH:3]=1.O.I([O-])(=O)(=O)=[O:28].[Na+].N1C(C)=CC=CC=1C>O1CCOCC1.[Os](=O)(=O)(=O)=O.O>[Cl:1][C:2]1[CH:3]=[CH:4][C:5]([CH:8]2[CH2:13][NH:12][C:11](=[O:14])[C:10]3[S:15][C:16]([N:20]4[CH2:25][CH2:24][O:23][CH2:22][CH2:21]4)=[C:17]([CH:18]=[O:28])[C:9]2=3)=[CH:6][CH:7]=1

Participants

8

Reactant 4

HCID 962WaterHCID 79372,6-LutidineHCID 23667635Sodium periodateHCID 68183169HCID 68183169, compound

Product 1

HCID 86669801HCID 86669801, compoundYield 84%

Reagents, catalysts & solvents 3

HCID 962WaterCatalystHCID 30318Osmium TetroxideCatalystHCID 312751,4-DioxaneSolvent

Conditions

Temperature
0 °C

Procedure

A suspension of 4-(4-chlorophenyl)-2-(morpholin-4-yl)-3-vinyl-5,6-dihydrothieno[2,3-c]pyridin-7(4H)-one (209.0 mg, 0.5575 mmol, single enantiomer of unknown configuration) in 1,4-dioxane (8.46 mL) and water (2.12 mL, 117 mmol) was cooled to 0° C. To the mixture was added sodium metaperiodate (0.477 g, 2.23 mmol), 2,6-lutidine (0.258 mL, 2.23 mmol), and a solution of 4% osmium tetroxide in water (68.1 uL, 0.0112 mmol). The reaction was vigorously stirred at 0° C. for 1 h. After 1 h, the ice-water bath was removed, and the reaction was stirred at rt for an hour. The reaction mixture was filtered through a celite pad, and the pad was washed with EtOAc. The filtrate was washed with 1N HCl (×2), brine, dried over Na2SO4, and concentrated in vacuo. The crude mixture was purified using column chromatography on silica gel (40 g ISCO column, continuous gradient 100% hexanes to 100% EA over 60 minutes) to give the title compound (176 mg orange oil, 84%). Final purification of 26 mg of this material by HPLC gave 16 mg pure product as a white solid. LCMS: (FA) ES+ 377, 379. 1H NMR (400 MHz, DMSO) δ 9.52 (s, 1H), 7.59 (d, J=4.5 Hz, 1H), 7.39-7.34 (m, 2H), 7.10-7.05 (m, 2H), 4.67 (d, J=4.4 Hz, 1H), 3.92 (dd, J=12.9, 5.1 Hz, 1H), 3.81-3.70 (m, 4H), 3.47-3.36 (m, 2H), 3.36-3.26 (m, 3H overlapping with H2O peak).

Workup

  1. waitAfter 1 h
  2. customthe ice-water bath was removed
  3. stirringthe reaction was stirred at rt for an hour
  4. filtrationThe reaction mixture was filtered through a celite pad
  5. washthe pad was washed with EtOAc
  6. washThe filtrate was washed with 1N HCl (×2), brine
  7. dry with materialdried over Na2SO4
  8. concentrationconcentrated in vacuo
  9. customThe crude mixture was purified
  10. customon silica gel (40 g ISCO column, continuous gradient 100% hexanes to 100% EA over 60 minutes)

Sources & evidence

ORD record
ord-779082446b684022982183d3c622ae45
Source dataset
uspto-grants-2014_07
Patent number
US08765746B2

Reaction notes

Loading…