Reaction #1702086

Reaction equation

5-(3,3-Dimethyl-but-1-ynyl)-3-[(1-methoxy-1-oxo-1λ5-phosphinan-4-yl)-(trans-4-methyl-cyclohexanecarbonyl)-amino]-thiophene-2-carboxylic acid

TMSBr

TMSBr

→

title compound

Yield 62.6%

5-(3,3-Dimethyl-but-1-ynyl)-3[(1-hydroxy-1-oxo-1 λ5phosphinan-4-yl)-(trans-4-methyl-cyclohexanecarbonyl)-amino]-thiophene-2-carboxylic acid

Yield 62.6%

Solvents

CH2Cl2

Conditions

Workup

1. 1
   workup.STIRRINGthe mixture was stirred at room temperature for 5 hours
2. 2
   Temperaturebefore cooling to 0° C.
3. 3
   Otherquenching through the addition of methanol (0.5 ml)
4. 4
   OtherThe solvent was removed under vacuum
5. 5
   Otherthe residue was purified by HPLC (Gemini column
6. 6
   Otherwater, 5 min
7. 7
   Otherwater, 18 min
8. 8
   Other100% acetonitrile, 6 min
9. 9
   workup.ADDITIONboth solvents containing 0.1% trifluoroacetic acid)

Procedure

5-(3,3-Dimethyl-but-1-ynyl)-3-[(1-methoxy-1-oxo-1λ5-phosphinan-4-yl)-(trans-4-methyl-cyclohexanecarbonyl)-amino]-thiophene-2-carboxylic acid (10 mg, 0.02 mmol) was dissolved in 1 mL of CH2Cl2, and to the solution was added TMSBr (26 μL, 0.2 mmol). The reaction mixture was stirred at room temperature for 40 minutes. Another portion of TMSBr (26 μL, 0.2 mmol) was added and the mixture was stirred at room temperature for 5 hours before cooling to 0° C. and quenching through the addition of methanol (0.5 ml). The solvent was removed under vacuum and the residue was purified by HPLC (Gemini column; 5% acetonitrile:water, 5 min; 5-100% acetonitrile:water, 18 min; 100% acetonitrile, 6 min; both solvents containing 0.1% trifluoroacetic acid). This resulted in 6 mg (62%) of the title compound. MS (m/z): 480.2 [M+H]+; HPLC retention time: 3.831 min (2-98% acetonitrile:water with 0.05% trifluoroacetic acid).

Source