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17th August 2016 @ 04:17

Methylation previously performed with Cs2CO3 in DMF (See: Synthesis of methyl 2-methoxy-2-phenylacetate (AEW 184-1)) which has led to low yields (~ 50% ). Use of silver oxide as a replacement is investigated here to determine if it will lead to an improvement of yields and/or efficiency. This method should also remove the risk of erosion of optical purity in enantiomerically pure substrates.

Literature reference :experimental details listed in the SI, page 23, 75% yield.

 

 

Experiment

To a solution of AEW 102 (1.00 g, 4.95 mmol, 1.00 equiv.) in dry dichloromethane (17 mL) was added methyl iodide (1.05 g, 0.462 mL, 7.42 mmol, 1.5) and silver oxide (1.64 g, 7.07 mmol, 1.43 equiv.).

The reaction mixture was stirred at room temperature for 24 h - still SM and new product by TLC. Stirred for two further days - no SM by TLC and filtered through a pad of Celite to yield a yellow oil in quantitative yield. Used directly in next reduction step.


Data

AEW 309-1 200 MHZ crude.png
AEW 309-1 200 MHZ crude.jcamp
AEW 309-1 200 MHZ crude.mnova
AEW 309-1 7:3 Petrol:EtOAc.JPG


Strings:

InChI=1S/C9H8F2O3/c1-14-9(13)8(12)5-2-3-6(10)7(11)4-5/h2-4,8,12H,1H3

to

InChI=1S/C10H10F2O3/c1-14-9(10(13)15-2)6-3-4-7(11)8(12)5-6/h3-5,9H,1-2H3

 

O=C(OC)C(O)C1=CC(F)=C(F)C=C1

to

O=C(OC)C(OC)C1=CC(F)=C(F)C=C1

Attached Files
AEW 309-1.png
AEW 309-1.cdxml
AEW 309-1 200 MHZ crude.png
AEW 309-1 200 MHZ crude.jcamp
AEW 309-1 200 MHZ crude.mnova
AEW 309-1.zip
AEW 309-1 7:3 Petrol:EtOAc.JPG
AEW 309-1 7:3 Petrol:EtOAc.JPG