Thionyl Chloride → HCID 9865407, compound

HRID 1635666Notes

Reaction equation

HRID 1635666 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 with 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 washed 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 with 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. washwashed 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-c3cc89042e934205afe4527f44d56d98
Source dataset
uspto-grants-2003_01
Patent number
US06509464B1

Reaction notes

Loading…