Reaktion #1702099

Reaktionsgleichung

5-(3,3-Dimethyl-but-1-ynyl)-3-[[2-(ethoxy-methyl-phosphinoyl)-ethyl]-(4-methyl-cyclohexanecarbonyl)-amino]-thiophene-2-carboxylic acid

TMSI

2,6-lutidine

→

5-(3,3-Dimethyl-but-1-ynyl)-3-[[2-(hydroxy-methyl-phosphinoyl)-ethyl]-(4-methyl-cyclohexanecarbonyl)-amino]-thiophene-2-carboxylic acid

Ausbeute 36.3%

Lösungsmittel

acetonitrile

Reaktionsbedingungen

Aufarbeitung

1. 1
   TemperaturThis solution was cooled in an ice bath
2. 2
   Sonstigesome precipitate was formed
3. 3
   Sonstigeresulting in a clear solution
4. 4
   SonstigeThe ice bath was removed
5. 5
   workup.ADDITIONAdditional TMSI (50 μL) and 2,6-lutidine (50 μL) were added
6. 6
   workup.WAITAfter 45 minutes the reaction was determined by LC/MS
7. 7
   TemperaturThe reaction was cooled in an ice bath
8. 8
   workup.ADDITIONadditional 2,6-lutidine (100 μL) was added
9. 9
   TemperaturThe reaction was warmed to room temperature
10. 10
    Einengenconcentrated under vacuum

Vorschrift

5-(3,3-Dimethyl-but-1-ynyl)-3-[[2-(ethoxy-methyl-phosphinoyl)-ethyl]-(4-methyl-cyclohexanecarbonyl)-amino]-thiophene-2-carboxylic acid (108 mg, 0.225 mmol) was dissolved in acetonitrile (3 mL). This solution was cooled in an ice bath and TMSI (160 μL, 1.12 mmol) was added dropwise. The reaction turned yellow and some precipitate was formed. After approximately 1 minute 2,6-lutidine (156 μL, 1.35 mmol) was added, resulting in a clear solution. The ice bath was removed and the reaction was stirred at room temperature for 2 hours. Additional TMSI (50 μL) and 2,6-lutidine (50 μL) were added. After 45 minutes the reaction was determined by LC/MS to be complete. The reaction was cooled in an ice bath and additional 2,6-lutidine (100 μL) was added, followed by MeOH (2 mL). The reaction was warmed to room temperature and concentrated under vacuum. 5-(3,3-Dimethyl-but-1-ynyl)-3-[[2-(hydroxy-methyl-phosphinoyl)-ethyl]-(4-methyl-cyclohexanecarbonyl)-amino]-thiophene-2-carboxylic acid (37 mg, 36%) was isolated from the residue by reverse phase HPLC. MS (m/z): 453.93 [M+H]+; 31P NMR (161.9 MHz, CD3OD): d 49.909.

Quelle