All Notebooks | Help | Support | About
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
4th October 2016 @ 20:30

Starting material, MRLS 2-3 (0.14g, 0.921 mmol), was added to a round bottom flask, and NBS (0.145g, 0.81 mmol, 0.9 eq) was added along with 10 ml of chloroform. Brought to reflux for 48 hours, then allowed to cool overnight. 

Workup: reaction mixture diluted with 20 mL more chloroform, then washed with 10 mL potassium carbonate. Aqueous layer washed with 2x10 mL chloroform and combined with the other organic layers. Solvent removed under reduced pressure. 

 

Log

10-1, 8:45p 

Reaction started. Everything was very soluble in chloroform as expected. Turned a dark wine color once everything was dissolved. Brought to reflux over about 20 minutes.

10-2

Took TLC of the reaction mixture (60% EtOAc) which showed a good bit of starting material left, so another 0.5 eq NBS was added. I noticed that it seemed like there was less chloroform than we'd started with, so I greased the joints of the reflux condenser and added 4 more mL chloroform to be on the safe side.

10-3

All of the chloroform is gone! It's kind of a mystery, because the argon balloon is still full. very hard solid was left in the flask. More chloroform added in hopes of salvaging the reaction. Most of the solid was soluble in chloroform, but there was some stuck to the stir bar that was insoluble. I took it off of the heat and let it cool over night, still stirring. 

10-4

Workup done as described above. Nothing good resulted. The aqueous and organic layers were quite difficult to distinguish, and there was a gooey slab in the aqueous layer. Organic layers concentrated anyways, giving a thick black oil. NMR was done in DMSO, which looked nothing like expected. Product scrapped.

Attached Files
3rd October 2016 @ 23:30

Started 9/24

Based on AEW 219-2.

 

Procedure:

MRLS 5-1 (5.2874 g, 31.8 mmol) and DHP were dissolved in anydrous CH2Cl2 under Argon in an ice bath. PPTS (0.2475 g, 0.96 mmol) was added to the reaction mixture. Left stirring in the ice bath for 5 hours. Then removed from ice bath and left stirring at room temperature for 17 hours. 

 

9/25

Work-up:

Poured mixture into a separatory funnel, and added 90 mL of DCM. Shook with portions of ice-cold H2O (15 mL X 3). Washed organic layers with 20 mL of NaHCO3. Dried with MgSO4, filtered, and then put under rotovap. Yield: 7.72 g, 97% yield. 

Took NMR and GC-MS.

GC-MS has many strange peaks-I suspect that the two large twin peaks might be diastereomers of the product (have similar fragments/mass peaks).

Attached Files
3rd October 2016 @ 23:20

This is the first step in the synthesis of 2-phenyl-2-tetrahydro-2H-pyran-2-yl)oxy)ethan-1-ol, needed to continue the next step of primary synthesis outlined in issue #430.

Procedure based off AEW 173-1.

(Started 9/21)

 

compound

MW (g/mol)

mol (mmol) g           density (g/mL) volume (mL) equivalents
DL-mandelic acid 152.15 32.9 5.010     1

p-TsOH

172.2 0.33 0.061     0.01
MeOH         66  
MRLS 5-1 166.18 32.9       1

Procedure:

Weighed out DL-mandelic acid (5.010 g, 33 mmol) into round bottom. Added 0.0610 g of p-TsOH and 66 mL of MeOH and stirred. Refluxed under Argon for 12 hours. 

(came in after ~6 hours to find the variac had turned off. Started the reflux again.)

TLC showed most of starting material was consumed. 

Removed solvent under reduced pressure and took NMR (96.6% yield, 31.8 mmol, 5.2874 g).

Used product as starting material for MRLS 6-1.

Attached Files
3rd October 2016 @ 22:44

Continuing primary synthesis using small amount of Synthesis of tert-butyl (E)-3-((2-(6-chloropyrazin-2-yl)hydrazono)methyl)piperidine-1-carboxylate (MRLS 3-1) without purification:

compound

MW (g/mol)

mol (mmol) g           density (g/mL) volume (mL) equivalents
MRLS 3-1 339.82 0.294 0.1     1

Diacetoxyiodobenzene

(PhI(OAc)2)

322.10 0.3 0.09663     1
CH2Cl2         3  
MRLS 4-1 337.81  0.294 0.0993     1

Procedure:

Stirred MRLS 3-1 (0.1010g, 0.294 mmol) in 3 mL of CH2Cl2 until completely dissolved. Added PhI(OAc)2 (0.1050 g, 0.3 mmol) and kept stirring the resultant mixture under Argon for 42 hours. 

 

9/17

Checked progress w/ TLC--starting material appeared to be consumed. Removed solvent via rotovap, giving an amber-colored oil. Left in hood overnight.

 

9/18

Purified crude product with flash column chromatography. Used 50% EtOAc in Hexanes as starting eluent, ran gradient up to 100%. 

Collected 28 fractions-- combined fractions 2-4 and rotovapped (yield: 0.0676 g, 68% yield). Left on high-vac overnight. 

 

Took NMR of the combined fractions--(attached on 10/27, sorry for the delay)

Attached Files