All Notebooks | Help | Support | About
19th November 2016 @ 19:12

deprotect.jpg
 
 
 

Compound

Mw (g/mol)

mmol

mL

g

equiv

Starting Material

526.6501

0.09494

 

50mg

1

HCl

38

0.0312

0.156 (2M HCl)

 

3.3

Product

Theoretical Values

339.17

0.09494

 

32.2

1

 

November 14, 2016

Procedure:

  1. Dissolve 50 mg of the starting material in 500 uL of anhydrous diethyl ether and place system under argon.

  2. Add 2M HCl-Ether (0.1 mL) dropwise to the solution while stirring.

  3. Age solution for 30 mins and the reaction was monitored with TLC.

IMAG0102.jpg

 

100% EtOAc solvent system, silica gel plate, UV visualization

S → Starting Material; C → Co-spot; P → Product

  1. The TLC of the reaction indicated that it was not complete, so another 500 uL of anhydrous ether and 50 uL of 2M HCl-ether was added to the reaction.

  2. The solution was then aged for another 30 minutes.

  3. TLC of the reaction was taken after the additional 30 minutes. Starting material was present, indicating the  reaction incomplete (presence of a salt). 500 uL of anhydrous ether was added to the reaction to ensure it remained in solution.

100% EtOAc solvent system, silica gel plate, UV visualization


S → Starting Material; C → Co-spot; P → Product

  1. The reaction was then gravity filtered and washed with diethyl ether to isolate the product. The product was a fine yellow solid.

 

November 16, 2016

Procedure

  1. The fine pale yellow solid was then mixed with diethyl ether (~8 mL) in a small r.b. Flask.

  2. Because the product was found to be insoluble in diethyl ether, it was put in a sonicator bath to speed up dissolution/resuspension.

  3. The mixture was left to settle in the r.b. A pale yellow, very fine solid settled  at the bottom of the flask.

  4. Vacuum filtration was done to separate the solid product from the diethyl ether. It was then washed once with diethyl ether to yield  0.0125g of final product.

  5. In preparation for NMR, 1 mL of methanol was added to 5 mg of the final product. (The final product (5 mg) was found to be insoluble in (1 mL) D2O, even after being put in the sonicator; this resulted in resuspension rather than dissolution).

  6. NMR and MS were run to determine presence of a salt and the identity of the product.

    (11/28/16)

  7. LCMS was run on the product and the spectrum is shown below:

     

    NemesisDeprotonationMassSpec.JPG
  8. Carbon and Proton NMR were run.

 

Conclusions:

 

The 440 peak on the MS and the terbutyl groups seen in the NMR suggest that we were not successful in removing BOC protecting group from the compound. The MS peak at 340, however, suggests that some of the BOC was successfully removed to form the correct final product. It is possible that the deprotection must be run longer to successfully remove all of the BOC protecting groups. 

Attached Files
14th November 2016 @ 16:54

11/9/16

Purification:

 
  1. The 550 mg of MSLR 9-1 was dry loaded onto silica and the product was purified using the biotage using a solvent system of 100% ETOAc.

  2. Fractions containing product were checked using TLC. TLC shows that the product was successfully isolated. In 3 fractions, high Rf impurities might be present in low concentration, however it is unclear and this will be addressed if the NMR looks messy.

  3. The product was concentrated in vacuo. Yield: 0.145 grams

100% EtOAc solvent system, silica gel plate, UV visualizationTLC100ethylacetatemarcolincoln9-1.jpg

The numbers at the bottom of the TLC plates are the factions we identified our product to be in.  The curve seen between the factions on the TLC suggests there are diastereomers present in our final product.

 
 

11/10/2016

4. Used HNMR to determine if THP and BOC groups were present in the product.

The tall peak at approximately 1.5 ppm suggests the presence of a BOC group (the 9H on the quaternary carbon at the end). The presence of peaks between 3-4 pm, as well as others around 1 ppm suggest THP is present .

 
purificationCarbonNMR.pdf
 
Conclusions:
 
It appears that the protecting groups are present. A deprotection step will be done to see if the final product is successfully synthesized.
Attached Files