Water → 4-[2-(2-Oxo-1,3-oxazolidin-3-yl)-1,3-thiazol-4-yl]benzonitrile

HRID 1436464Notes

Reaction equation

HRID 1436464 reaction equation
[NH2:1][C:2]1[S:3][CH:4]=[C:5]([C:7]2[CH:14]=[CH:13][C:10]([C:11]#[N:12])=[CH:9][CH:8]=2)[N:6]=1.[H-].[Na+].Cl[C:18]([O:20][CH2:21][CH2:22]Cl)=[O:19].O>O1CCCC1>[O:19]=[C:18]1[N:1]([C:2]2[S:3][CH:4]=[C:5]([C:7]3[CH:8]=[CH:9][C:10]([C:11]#[N:12])=[CH:13][CH:14]=3)[N:6]=2)[CH2:22][CH2:21][O:20]1

Participants

6

Reactant 4

HCID 962WaterHCID 123052-Chloroethyl chloroformateHCID 24758Sodium hydrideHCID 20495894-(2-Amino-1,3-thiazol-4-yl)benzonitrile

Product 1

HCID 250287154-[2-(2-Oxo-1,3-oxazolidin-3-yl)-1,3-thiazol-4-yl]benzonitrileYield 10%

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent2×

Procedure

4-(2-Amino-thiazol-4-yl)-benzonitrile (1.5 g, 7.4 mmol), prepared in the previous step, in dry tetrahydrofuran (10 mL) was added dropwise to a suspension of sodium hydride (0.6 g, ˜15 mmol, 60% in oil) in dry tetrahydrofuran (10 mL) at room temperature. After 1 h, 2-chloroethyl chloroformate (0.83 mL, 8 mmol) was added dropwise and the mixture heated under reflux. After 16 h, the mixture was cooled, poured carefully into water, which was extracted with ethyl acetate. The organic layer was separated, dried (anhydrous Na2SO4), evaporated and the residue purified by silica gel column chromatography (ethyl acetate:hexane, 3:7) to afford the crude product. Recrystallization from ethanol gave the title compound (0.2 g, 10%), MS (ES) m/z 272 [M+H]+. HPLC 99.5% @ 210-370 nm, 99.3% @ 240 nm; RT=8.3 min, the Xterra® RP18 column, 3.5μ, 4.6×150 mm column 1.2 mL/min, 85/15-5/95 (Phos Buff. pH=2.1/ACN+MeOH) for 10 min, hold 4 min.

Workup

  1. temperaturethe mixture heated
  2. temperatureunder reflux
  3. waitAfter 16 h
  4. temperaturethe mixture was cooled
  5. extractionwas extracted with ethyl acetate
  6. customThe organic layer was separated
  7. dry with materialdried (anhydrous Na2SO4)
  8. customevaporated
  9. customthe residue purified by silica gel column chromatography (ethyl acetate:hexane, 3:7)
  10. customto afford the crude product
  11. customRecrystallization from ethanol

Sources & evidence

ORD record
ord-060c9f80f0db4b8e886258ff5985bf93
Source dataset
uspto-grants-2009_11
Patent number
US07618990B2

Reaction notes

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