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20th April 2016 @ 03:15

Procedure:

AEW 205-6 (500 mg, 1.69 mmol, 1.00 equiv.), AEW 287-1 (398 mg, 1.96 mmol, 1.00 equiv.), potassium hydroxide (331 mg, 5.90 mmol, 3.50 equiv.) and 18-crown-6 (31 mg, 0.12 mmol, 0.07 equiv.) were dissolved in toluene (32 mL) and heated to 40 ˚C for 30 min. Turned black on addition of nucleophile.

TLC showed new spot and SM and so stirred for further 40 min at 40 ˚C.

Water (30 mL) was added to the reaction mixture and diluted with EtOAc (30 mL). Organic layers were separated and the aqueous layer extracted with EtoAc (3 x 30 mL). Combined organic layers were washed with water (20 mL), brine (20 mL) and then dried (MgSO4), filtered and evaporated to give a brown oil. Aqueous layers were re-extracted - need to improve w-up for these reactions as suspension results. Brown oil combined with original.

Purified using Biotage IsoleraTM, hand packed 100 g colum EtOAc/Hex gradient.

One fraction collected - yellow/brown oil (164 mg, 0.33 mmol, 20% yield)

 

TLC Datat:

 

NMR:

AEW 289-1 PURIFIED.png
AEW 289-1 purified.dx
AEW 289-1 crude.zip

Strings:

InChI=1S/C12H7ClF2N4O/c13-9-5-16-6-10-17-18-11(19(9)10)7-1-3-8(4-2-7)20-12(14)15/h1-6,12H

and

InChI=1S/C14H20O3/c15-10-13(12-6-2-1-3-7-12)11-17-14-8-4-5-9-16-14/h1-3,6-7,13-15H,4-5,8-11H2

to

InChI=1S/C26H26F2N4O4/c27-26(28)36-21-11-9-19(10-12-21)25-31-30-22-14-29-15-23(32(22)25)34-16-20(18-6-2-1-3-7-18)17-35-24-8-4-5-13-33-24/h1-3,6-7,9-12,14-15,20,24,26H,4-5,8,13,16-17H2

ClC1=CN=CC2=NN=C(C3=CC=C(OC(F)F)C=C3)N21

and

OCC(COC1OCCCC1)C2=CC=CC=C2

to

FC(OC(C=C1)=CC=C1C2=NN=C3N2C(OCC(C4=CC=CC=C4)COC5OCCCC5)=CN=C3)F

Attached Files
AEW279-1.mol
AEW 289-1.rxn
AEW 289-1.png
AEW 289-1 PURIFIED.png
AEW 289-1 purified.dx
AEW 289-1 crude.zip
Comments
Re: Synthesis of 3-(4-(difluoromethoxy)phenyl)-5-(2-phenyl-3-((tetrahydro-2H-pyran-2-yl)oxy)propoxy)-[1,2,4]triazolo[4,3-a]pyrazine (AEW 289-1) by George O'Hara
17th November 2017 @ 01:00
Hello Alice, my name is George O'Hara, I am a student at Haverford College in the U.S. attempting this reaction. I cannot find your TLC photo. Which file is this in?

Best,

George O'Hara