Triethylamine → HCID 90202312, compound

HRID 929760Notes

Reaction equation

HRID 929760 reaction equation
[C:1]([Si:5]([CH3:17])([CH3:16])[O:6][C:7]1[CH:15]=[CH:14][C:10]([CH:11]=[N:12][OH:13])=[CH:9][CH:8]=1)([CH3:4])([CH3:3])[CH3:2].ClN1C(=O)CCC1=O.[C:26]([O:30][CH2:31][CH3:32])(=[O:29])[C:27]#[CH:28].C(N(CC)CC)C>CN(C=O)C.CCOCC>[CH2:31]([O:30][C:26]([C:27]1[O:13][N:12]=[C:11]([C:10]2[CH:14]=[CH:15][C:7]([O:6][Si:5]([C:1]([CH3:4])([CH3:3])[CH3:2])([CH3:17])[CH3:16])=[CH:8][CH:9]=2)[CH:28]=1)=[O:29])[CH3:32]

Participants

7

Reactant 4

HCID 8471TriethylamineHCID 12182Ethyl propiolateHCID 31398ChlorosuccinimideHCID 76780050HCID 76780050, compound

Product 1

HCID 90202312HCID 90202312, compoundYield 2%

Reagents, catalysts & solvents 2

HCID 3283Diethyl EtherSolventHCID 6228DimethylformamideSolvent

Conditions

Temperature
0 °C

Procedure

4-(tert-Butyl-dimethyl-silanyloxy)-benzaldehyde oxime (which may be prepared according to the procedure described in Kao, Y. T. R. et al. US 20110212975 page 17; ˜20 g, ˜80 mmol) was dissolved in DMF (50 mL) and the solution was cooled to 0° C. N-Chlorosuccinimide (12.8 g, 96 mmol) was added in portions. The reaction mixture was stirred at 0° C. for 30 min, allowed to warm to room temperature and stirred at room temperature for 1.5 h. The reaction mixture was poured into ice-water (100 mL) and the resulting suspension was extracted with EtOAc (100 mL). The organic extract was dried over Na2SO4, filtered, and evaporated. Et2O (120 mL) was added to the residue, and then a solution of ethyl propiolate (16 mL, 158 mmol) and triethylamine (12 mL) in Et2O (120 mL) was added dropwise. The mixture was stirred at room temperature for 48 h. The reaction mixture was filtered and the filtrate was evaporated to give a brown oil which was purified by filtration through a silica gel plug (eluting with 12% EtOAc/hexanes) followed by silica gel chromatography. Final purification was accomplished using preparatory supercritical fluid chromatography (100 bar CO2 modified with 10% MeOH, flow rate of 2 mL/min at 30° C.) to give 3-[4-(tert-butyl-dimethyl-silanyloxy)-phenyl]-isoxazole-5-carboxylic acid ethyl ester (600 mg, 2%).

Workup

  1. temperatureto warm to room temperature
  2. stirringstirred at room temperature for 1.5 h
  3. extractionthe resulting suspension was extracted with EtOAc (100 mL)
  4. extractionThe organic extract
  5. dry with materialwas dried over Na2SO4
  6. filtrationfiltered
  7. customevaporated
  8. additionEt2O (120 mL) was added to the residue
  9. stirringThe mixture was stirred at room temperature for 48 h
  10. filtrationThe reaction mixture was filtered
  11. customthe filtrate was evaporated
  12. customto give a brown oil which
  13. filtrationwas purified by filtration through a silica gel plug (eluting with 12% EtOAc/hexanes)
  14. customFinal purification
  15. customsupercritical fluid chromatography (100 bar CO2 modified with 10% MeOH, flow rate of 2 mL/min at 30° C.)

Sources & evidence

ORD record
ord-55e054750e5848fa9c1d40a77c1d428e
Source dataset
uspto-grants-2016_03
Patent number
US09296711B2

Reaction notes

Loading…