Thionyl Chloride → HCID 9865407, compound

HRID 1276183Notes

Reaction equation

HRID 1276183 reaction equation
S[C:2]1[O:3][C:4]2[C:10]([C:11]([O:13][CH3:14])=[O:12])=[CH:9][CH:8]=[CH:7][C:5]=2[N:6]=1.S(Cl)(Cl)=O.C(N(C(C)C)C(C)C)C.[Cl-].[CH2:29]([O:36][C:37]([C@@H:39]1[CH2:44][CH2:43][CH2:42][CH2:41][NH2+:40]1)=[O:38])[C:30]1[CH:35]=[CH:34][CH:33]=[CH:32][CH:31]=1>C(#N)C.CN(C)C=O>[CH3:14][O:13][C:11]([C:10]1[C:4]2[O:3][C:2]([N:40]3[CH2:41][CH2:42][CH2:43][CH2:44][C@H:39]3[C:37]([O:36][CH2:29][C:30]3[CH:35]=[CH:34][CH:33]=[CH:32][CH:31]=3)=[O:38])=[N:6][C:5]=2[CH:7]=[CH:8][CH:9]=1)=[O:12]

Participants

7

Reactant 4

HCID 24386Thionyl ChlorideHCID 81531DiisopropylethylamineHCID 86591486(2S)-2-((benzyloxy)carbonyl]piperidinium chlorideHCID 178497587HCID 178497587, compound

Product 1

HCID 9865407HCID 9865407, compoundYield 23.4%

Reagents, catalysts & solvents 2

HCID 6228DimethylformamideSolventHCID 6342AcetonitrileSolvent

Procedure

2-Sulfanyl-7-(methoxy)carbonyl-1,3-benzoxazole (1.00 g) [see Preparation 49] was added to thionyl chloride (4.9 ml) followed by dimethylformamide (0.37 ml) and the mixture heated at reflux for 10 minutes. The mixture was cooled and the solvent removed at reduced pressure, the residue was azeotroped twice the xylene to afford a tan solid. This solid was immediately dissolved in acetonitrile (20 ml) and N-ethyldiisopropylamine (3.3 ml) and (2S)-2-[(benzyloxy)carbonyl]piperidinium chloride (1.22 g) was added and the mixture was then heated at reflux for 7 hours. The reaction was cooled, the solvent removed at reduced pressure, and the residue dissolved in ethyl acetate and wash sequentially with 1M aqueous citric acid solution, saturated aqueous sodium hydrogen carbonate solution, brine, then dried over magnesium sulfate and the solvent removed at reduced pressure. The crude product was purified by column chromatography on silica gel eluting with a solvent gradient of 5:1, by volume, hexane:ethyl acetate to afford benzyl (2S)-1-[7-(methoxy)carbonyl-1,3-benzoxazol-2-yl]-2-piperidinecarboxylate (0.44 g) as an orange gum.

Workup

  1. temperaturethe mixture heated
  2. temperatureat reflux for 10 minutes
  3. temperatureThe mixture was cooled
  4. customthe solvent removed at reduced pressure
  5. customthe residue was azeotroped twice the xylene
  6. customto afford a tan solid
  7. temperaturethe mixture was then heated
  8. temperatureat reflux for 7 hours
  9. temperatureThe reaction was cooled
  10. customthe solvent removed at reduced pressure
  11. dissolutionthe residue dissolved in ethyl acetate
  12. washwash sequentially with 1M aqueous citric acid solution, saturated aqueous sodium hydrogen carbonate solution, brine
  13. dry with materialdried over magnesium sulfate
  14. customthe solvent removed at reduced pressure
  15. customThe crude product was purified by column chromatography on silica gel eluting with a solvent gradient of 5:1, by volume, hexane

Sources & evidence

ORD record
ord-f5e4d9bc7d0e482daf05cba14d5cb60b
Source dataset
uspto-grants-2000_12
Patent number
US06166011

Reaction notes

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