3,3-Diethoxypropyne → (S)-N-[[3-[3-Fluoro-4-(4-(diethoxymethyl)-1H-1,2,3-triazol-1-yl)phenyl]-2-oxo-5-oxazoldinyl]methyl]acetamide

HRID 1415904Notes

Reaction equation

HRID 1415904 reaction equation
[N:1]([C:4]1[CH:9]=[CH:8][C:7]([N:10]2[CH2:14][C@H:13]([CH2:15][NH:16][C:17](=[O:19])[CH3:18])[O:12][C:11]2=[O:20])=[CH:6][C:5]=1[F:21])=[N+:2]=[N-:3].[CH2:22]([O:24][CH:25]([O:28][CH2:29][CH3:30])[C:26]#[CH:27])[CH3:23]>C1C=CC=CC=1>[F:21][C:5]1[CH:6]=[C:7]([N:10]2[CH2:14][C@H:13]([CH2:15][NH:16][C:17](=[O:19])[CH3:18])[O:12][C:11]2=[O:20])[CH:8]=[CH:9][C:4]=1[N:1]1[CH:27]=[C:26]([CH:25]([O:28][CH2:29][CH3:30])[O:24][CH2:22][CH3:23])[N:3]=[N:2]1

Participants

4

Reactant 2

HCID 662853,3-Diethoxypropyne2×HCID 10708829(S)-N-[[3-[4-Azido-3-fluorophenyl]-2-oxo-5-oxazolidinyl]methyl]acetamide

Product 1

HCID 53941020(S)-N-[[3-[3-Fluoro-4-(4-(diethoxymethyl)-1H-1,2,3-triazol-1-yl)phenyl]-2-oxo-5-oxazoldinyl]methyl]acetamideYield 81.8%

Reagents, catalysts & solvents 1

HCID 241BenzeneSolvent

Procedure

A solution of 1.70 g (5.8 mmol) of the azide of example 17 in 50 mL benzene was treated with 4.46 g (34.8 mmol) of 1,1-diethoxy-2-propyne followed by warming at reflux for 18 h. The solution was treated with 1.0 g (7.80 mmol) of 1,1-diethoxy-2-propyne followed by warming at reflux for an additional 3 h. The solution was cooled and concentrated in vacuo to afford an oil which was chromatographed over 200 g of 230-400 mesh silica gel, eluting with 2-3% (v/v) methanol in dichloromethane to afford 2.0 g (80%) of (S)-N-[[3-[3-Fluoro-4-(4-(diethoxymethyl)-1H-1,2,3-triazol-1-yl)phenyl]-2-oxo-5-oxazoldinyl]methyl]acetamide and (S)-N-[[3-[3-Fluoro-4-(5-(diethoxymethyl)-1H-1,2,3-triazol-1-yl)phenyl]-2-oxo-5-oxazoldinyl]methyl]acetamide as an inseparable mixture of isomers. Of this material, 410 mg (0.973 mmol) was dissolved in 10 mL THF and treated with 1 mL of 1N HCl solution followed by stirring at ambient temperature for 48 h, and then warming at reflux for 1 h. The mixture was dissolved in ethyl acetate and extracted with water. Drying (Na2SO4) and concentration in vacuo afforded an oil which was subjected to radial chromatography on a 2 mm chromatotron plate eluting with 7% (v/v) methanol in dichloromethane. The less polar fraction [110 mg (33%)] from the chromatography proved to be the title compound, isolated as a white solid. 1H NMR (CDCl3) δ 8.60, 7.99, 7.85, 7.36, 6.1, 4.86, 4.12, 3.89, 3.72, 2.04.

Workup

  1. temperatureby warming
  2. temperatureat reflux for 18 h
  3. temperatureby warming
  4. temperatureat reflux for an additional 3 h
  5. temperatureThe solution was cooled
  6. concentrationconcentrated in vacuo
  7. customto afford an oil which
  8. customwas chromatographed over 200 g of 230-400 mesh silica gel
  9. washeluting with 2-3% (v/v) methanol in dichloromethane

Sources & evidence

ORD record
ord-ba0ed106a1d84bde87b520df0267694f
Source dataset
uspto-grants-1999_06
Patent number
US05910504

Reaction notes

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