반응 #1702099

반응 방정식

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

수율 36.3%

용매

acetonitrile

반응 조건

후처리

1. 1
   온도This solution was cooled in an ice bath
2. 2
   기타some precipitate was formed
3. 3
   기타resulting in a clear solution
4. 4
   기타The 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
   온도The reaction was cooled in an ice bath
8. 8
   workup.ADDITIONadditional 2,6-lutidine (100 μL) was added
9. 9
   온도The reaction was warmed to room temperature
10. 10
    농축concentrated under vacuum

실험 절차

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.

출처