反应 #1702099

反应方程式

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

收率 36.3%

溶剂

acetonitrile

反应条件

后处理

1. 1
   温度This solution was cooled in an ice bath
2. 2
   其他some precipitate was formed
3. 3
   其他resulting in a clear solution
4. 4
   其他The 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
   温度The reaction was cooled in an ice bath
8. 8
   workup.ADDITIONadditional 2,6-lutidine (100 μL) was added
9. 9
   温度The reaction was warmed to room temperature
10. 10
    浓缩concentrated under vacuum

实验过程

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.

来源