Sodium hydride → HCID 89713636, compound

HRID 1518970Notes

Reaction equation

HRID 1518970 reaction equation
[H-].[Na+].[O:3]=[C:4]1[CH2:9][CH2:8][N:7]([C:10]([O:12][C:13]([CH3:16])([CH3:15])[CH3:14])=[O:11])[CH2:6][CH2:5]1.Cl[C:18]1[S:19][CH:20]=[CH:21][N:22]=1>>[O:3]=[C:4]1[CH2:5][CH2:6][N:7]([C:10]([O:12][C:13]([CH3:16])([CH3:15])[CH3:14])=[O:11])[CH2:8][CH:9]1[C:18]1[S:19][CH:20]=[CH:21][N:22]=1

Participants

4

Reactant 3

HCID 24758Sodium hydrideHCID 764292-ChlorothiazoleHCID 735900tert-Butyl 4-oxopiperidine-1-carboxylate

Product 1

HCID 89713636HCID 89713636, compoundYield 23.5%

Procedure

Add sodium hydride (3.61 g, 90.3 mmol) to a solution of tert-butyl 4-oxopiperidine-1-carboxylate (12.0 g, 60.2 mmol) and stir for one hour at ambient temperature. Add 2-chlorothiazole (7.92 g, 66.3 mmol) and stir one additional hour at ambient temperature. Heat to reflux and stir for 14 hours at reflux. Cool mixture to ambient temperature and quench with sufficient HCl (2N) to adjust the pH of the mixture to less than 5. Extract the mixture three times with EtOAc; combine the organic extracts; sequentially wash with water then brine; dry over magnesium sulphate; filter; collect the filtrate; and then concentrate under vacuum at 40° C. Purify the crude material by silica gel flash column chromatography eluting with 10% EtOAc in hexane to give the title compound as a white solid (4.0 g, 23.5%). 1HNMR (d6-DMSO) δ 1.3 (s, 9H), 2.3-2.5 (m, 2H), 3.5 (t, J=6.1 Hz, 2H), 4.1-4.3 (m, 3H), 7.5 (s, 1H), 7.7 (s, 1H).

Workup

  1. temperatureHeat
  2. temperatureto reflux
  3. stirringstir for 14 hours
  4. temperatureat reflux
  5. temperatureCool mixture to ambient temperature
  6. customquench with sufficient HCl (2N)
  7. extractionExtract the mixture three times with EtOAc
  8. washsequentially wash with water
  9. dry with materialdry over magnesium sulphate
  10. filtrationfilter
  11. customcollect the filtrate
  12. concentrationand then concentrate under vacuum at 40° C
  13. customPurify the crude material by silica gel flash column chromatography
  14. washeluting with 10% EtOAc in hexane

Sources & evidence

ORD record
ord-ae5375509cdf48399e5f3aec94b98763
Source dataset
uspto-grants-2015_07
Patent number
US09073856B2

Reaction notes

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