Hydrochloric Acid → HCID 136011268, compound

HRID 1349867Notes

Reaction equation

HRID 1349867 reaction equation
[F:1][C:2]1[CH:7]=[CH:6][C:5]([C:8]2[C:16]3[C:11](=[CH:12][CH:13]=[C:14]([C:17]4[NH:21][C:20](=[O:22])[O:19][N:18]=4)[CH:15]=3)[N:10](C3CCCCO3)[N:9]=2)=[CH:4][CH:3]=1.Cl.[OH-].[Na+]>O1CCOCC1.CO>[F:1][C:2]1[CH:7]=[CH:6][C:5]([C:8]2[C:16]3[C:11](=[CH:12][CH:13]=[C:14]([C:17]4[NH:21][C:20](=[O:22])[O:19][N:18]=4)[CH:15]=3)[NH:10][N:9]=2)=[CH:4][CH:3]=1

Participants

7

Reactant 3

HCID 313Hydrochloric Acid3×HCID 14798Sodium HydroxideHCID 136376435HCID 136376435, compound

Product 1

HCID 136011268HCID 136011268, compoundYield 19.1%

Reagents, catalysts & solvents 3

HCID 887MethanolCatalystHCID 887MethanolSolventHCID 312751,4-DioxaneSolvent2×

Procedure

To a solution of 3-[3-(4-fluorophenyl)-1-perhydro-2H-pyran-2-yl-1H-indazol-5-yl]-1,2,4-oxadiazolin-5-one (88 mg, 0.23 mmol) in dioxane (4.0 mL) was added 6 N HCl (4.0 mL) at ambient temperature. After stirring for 16 h an additional amount of dioxane (1.0 mL) was added and the reaction mixture was gently heated in a 60° C. oil bath for 4 h after which an additional amount of 6 N HCl (1.0 mL) and several drops of methanol were added and after an additional 4 h of heating the reaction was stopped by slowly pouring into vigorously stirred aqueous 6 N NaOH (6.0 mL). The solution was adjusted to pH=8 with the addition of 4 N HCl and extracted with ethyl acetate. The organic layer was washed with brine, dried over MgSO4 and concentrated in vacuo to give a pale orange solid which was purified by flash chromatography on silica gel eluting with 10% methanol in dichloromethane to give a pale yellow solid which was dissolved in a minimum amount of methanol and precipitated with ethyl ether and hexanes to afford the desired product as a pale powder (13 mg, 19% yield) 1H NMR (DMSO-d6): δ 13.6 (s, 1H), 13.0 (br s, 1H), 8.5 (s, 1H), 8.1–8.0 (m, 2H), 7.8 (q, 2H), 7.3 (t, 2H); ES-MS (m/z) 297 [M+H]+.

Workup

  1. additionwas added
  2. additionwere added and after an additional 4 h
  3. temperatureof heating the reaction
  4. extractionextracted with ethyl acetate
  5. washThe organic layer was washed with brine
  6. dry with materialdried over MgSO4
  7. concentrationconcentrated in vacuo
  8. customto give a pale orange solid which
  9. customwas purified by flash chromatography on silica gel eluting with 10% methanol in dichloromethane
  10. customto give a pale yellow solid which
  11. customprecipitated with ethyl ether and hexanes

Sources & evidence

ORD record
ord-a0517211882647b894247ceddf84ab11
Source dataset
uspto-grants-2007_05
Patent number
US07211594B2

Reaction notes

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