Sodium hydride → HCID 67237093, compound

HRID 2364812Notes

Reaction equation

HRID 2364812 reaction equation
[Br:1][C:2]1[CH:22]=[CH:21][C:5]2[NH:6][C:7]([C@@H:9]3[CH2:13][CH2:12][CH2:11][N:10]3[C:14]([O:16][C:17]([CH3:20])([CH3:19])[CH3:18])=[O:15])=[N:8][C:4]=2[CH:3]=1.[H-].[Na+].[CH3:25][Si:26]([CH2:29][CH2:30][O:31][CH2:32]Cl)([CH3:28])[CH3:27]>C1COCC1>[Br:1][C:2]1[CH:22]=[CH:21][C:5]2[N:6]=[C:7]([C@@H:9]3[CH2:13][CH2:12][CH2:11][N:10]3[C:14]([O:16][C:17]([CH3:19])([CH3:18])[CH3:20])=[O:15])[N:8]([CH2:32][O:31][CH2:30][CH2:29][Si:26]([CH3:28])([CH3:27])[CH3:25])[C:4]=2[CH:3]=1

Participants

5

Reactant 3

HCID 24758Sodium hydrideHCID 27242712-Chloromethyl 2-(trimethylsilyl)ethyl etherHCID 178451891HCID 178451891, compound

Product 1

HCID 67237093HCID 67237093, compoundYield 73.5%

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent

Procedure

A solution of the compound of Example 49B (2.25 g, 6.14 mmol) in dry THF (25 mL) was treated with sodium hydride (295 mg of 60% in oil, 177 mg, 7.37 mmol) followed by stirring at room temperature for 1 h. The solution was then treated with SEM-Chloride (1.20 mL, 1.13 g, 6.76 mmol) followed by stirring at room temperature for 18 h. The mixture was quenched by addition of water and the mixture was diluted with ethyl acetate. The mixture was extracted with water and saturated sodium chloride solution. Drying (Na2SO4) and concentration in vacuo afforded an oil, which was chromatographed over a 100 g silica gel cartridge, eluting with 20-75% ethyl acetate in hexanes. These procedures afforded the product (2.24 g, 73%) as a heavy oil, which solidified after setting for several days. This mixture of both regioisomeric SEM derivatives was not separated for use in the next step.

Workup

  1. stirringby stirring at room temperature for 18 h
  2. customThe mixture was quenched by addition of water
  3. additionthe mixture was diluted with ethyl acetate
  4. extractionThe mixture was extracted with water and saturated sodium chloride solution
  5. customDrying
  6. concentration(Na2SO4) and concentration in vacuo
  7. customafforded an oil, which
  8. customwas chromatographed over a 100 g silica gel cartridge
  9. washeluting with 20-75% ethyl acetate in hexanes

Sources & evidence

ORD record
ord-3c76ec8b6df14612acfad110f2ef24a1
Source dataset
uspto-grants-2014_04
Patent number
US08691938B2

Reaction notes

Loading…