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21st September 2016 @ 03:36

NB used crude AEW 232-3 prior to NMR owing to time constraints - will check validity of SM asap.

 

 

AEW 232-3 (based on 1.96 mmol) was dissolved in EtOH (8 mL). CuCl2.2H2O (17 mg, 0.08 mmol, 5 mol%) was added and the reaction heated at reflux for 40 mins. TLC no SM

The solvent was removed and the crude black oil was columned using the Biotage Isolera - EtOAc then 10-20% MeOH in DCM. Multiple black fractions collected.

 

Data:

TLC

AEW 317-1 (EtOAc).JPG

AEW 317-1 Frac 2 NMR 300 MHz

problem accessing NMR data but looks promising

Strings:

FC(OC(C=C1)=CC=C1C2=NN=C3N2C(OCC(COC4OCCCC4)C5=CC=CC=C5)=CN=C3)F

to

OCC(C1=CC=CC=C1)COC2=CN=CC3=NN=C(C4=CC=C(OC(F)F)C=C4)N32

InChI=1S/C21H18F2N4O3/c22-21(23)30-17-8-6-15(7-9-17)20-26-25-18-10-24-11-19(27(18)20)29-13-16(12-28)14-4-2-1-3-5-14/h1-11,16,21,28H,12-13H2

to

InChI=1S/C21H18F2N4O3/c22-21(23)30-17-8-6-15(7-9-17)20-26-25-18-10-24-11-19(27(18)20)29-13-16(12-28)14-4-2-1-3-5-14/h1-11,16,21,28H,12-13H2

Attached Files
21st September 2016 @ 00:14

 

Procedure:

To a solution of oxalyl chloride (5.42 mL, 63.2 mmol, 5 equiv.) and 3 Å MS in CH2Cl2 (13 mL) at -78 °C under N2 was added dropwise a solution of DMSO (8.98 mL, 126 mmol) in CH2Cl2 (1 mL). After 15 min a solution of the alcohol (2.00 g, 12. 7 mmol, 1 equiv.) in CH2Cl2 (40 mL) was slowly added dropwise. After 30 min, Et3N (26.4 mL, 190 mmol) was added dropwise. The reaction was stirred 30 min at -78 °C then slowly allowed to warm to rt whilst stirring for 20 h.

TLC inconclusive

Reaction partioned with 1M HCl (aq) and organic layers extracted and then washed with 1M HCl (aq) x 2, a saturated aqueous solution of NaHCO(x 3), water, brine and then dried over MgSO4 filtered and evaporated to give a yellow oil. Crude NMR shows mixture of products.

TLC of crude shows one major product and faint other spots - one that can be seen more clearly when visualised with KMnO4.

Purified using the Biotage Isolera (10% EtOAc in Hexane gradient, 50 g handpacked column) to yield two products:

Frac 1 - bright yellow liquid - desired product

Frac 2 - bright yellow oil - starting material

 

Data:

TLC: AEW 316-1 (10% EtOAc in Hex) after work-up

AEW 316-1 (10% EtOAc in Hex) after work-up.JPG

Crude NMR 300 MHz:

 

Strings:

FC1=C(F)C=C(C(O)C)C=C1

to

FC1=C(F)C=C(C(C)=O)C=C1

InChI=1S/C8H8F2O/c1-5(11)6-2-3-7(9)8(10)4-6/h2-5,11H,1H3

to

InChI=1S/C8H6F2O/c1-5(11)6-2-3-7(9)8(10)4-6/h2-4H,1H3


Literature Reference:

http://www.ochemonline.com/Swern_oxidation

Attached Files
20th September 2016 @ 05:49

 

AEW 205 (500 mg, 1.96 mmol, 1 equiv) was suspended in anhydrous toluene (10 mL) along with potassium hydroxide (384 mg, 6.84 mmol, 3.5 equiv) and 18-crown-6 (36 mg, 0.14 mmol, 0.07 equiv). AEW 287-2 (435 mg, 0.67 mmol, 1 equiv) was dissolved in anhydrous toluene and added to the reaction mixture whilst stirring at rt for ten mins. Reaction heated to 40 ˚C with stirring.

After 1h, still SM

EtOAc 1 h.jpeg

The sample was cooled to room temperature and diluted with 10 mL of water. The mixture was extracted with EtOAc (3 x 20 mL). The combined organic layer was washed with water (1 x 10 mL) until the aqueous layer became neutral followed by brine (6 mL) and dried over Na2SO4. The orange/yellow fluoro solution was filtered and dried under reduced pressure and in vacuo to yield an orange oil that was dried at the high vac.

 

Data:


InChi:

InChI=1S/C11H9ClF2N4O/c1-7(3-2-4-19-11(13)14)10-17-16-9-6-15-5-8(12)18(9)10/h2-3,5-6,11H,1,4H2/b3-2-

and

InChI=1S/C13H18O3/c14-10-12(11-6-2-1-3-7-11)16-13-8-4-5-9-15-13/h1-3,6-7,12-14H,4-5,8-10H2

to

InChI=1S/C25H24F2N4O4/c26-25(27)34-19-11-9-18(10-12-19)24-30-29-21-14-28-15-22(31(21)24)33-16-20(17-6-2-1-3-7-17)35-23-8-4-5-13-32-23/h1-3,6-7,9-12,14-15,20,23,25H,4-5,8,13,16H2


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

and

OCC(OC1OCCCC1)C2=CC=CC=C2

to

FC(F)OC(C=C1)=CC=C1C2=NN=C3N2C(OCC(OC4OCCCC4)C5=CC=CC=C5)=CN=C3

Attached Files
20th September 2016 @ 04:26



Procedure

3,4-difluorobenzaldehyde (2.00 g, 14.1 mmol, 1.00 equiv.) was dissolved in anhydrous ether (28 mL) and then stirred at 0 ˚C. MeMgBr (4.74 mL, 14.2 mmol, 1.01 equiv, 3.0 M in THF) (colourless to pale yellow soln) and the reaction mixture stirred at 0˚C for 5 min and then allowed to warm to rt and stirred for 30 mins.

TLC showed no SM (30% EtOAc in Hexane)

30%EtOAc in Hexane.jpeg

Reaction mixture cooled to 0 ˚C and then a saturated solution of 1 M HCl (20 mL) added dropwise with stirring (no vigourous reaction). Volatiles were removed in vacuo to give a yellow ppt. Reaction mixture partioned between EtOAc (40 mL) and a saturated solution of ammonium chloride (40 mL) and then layers separated. Aqueous washed with EtOAc (2 x 30 mL) and then combined organic washed with water (20 mL), brine (20 mL), dried (MgSO4), filtered and evaporated to give a pale pink liquid (2.00 g, 12.7 mmol, 90% crude yield) which was used as crude in the subsequent Swern Oxidation. 

 

Data:

200 MHz NMR in CDCl3

AEW 315-1 Proton.png
AEW 315-1 Proton.jcamp
AEW 315-1 Proton.mnova

Strings

O=CC1=CC(F)=C(F)C=C1

to

FC1=C(F)C=C(C(O)C)C=C1

InChI=1S/C7H4F2O/c8-6-2-1-5(4-10)3-7(6)9/h1-4H

to

InChI=1S/C8H8F2O/c1-5(11)6-2-3-7(9)8(10)4-6/h2-5,11H,1H3

Attached Files
12th September 2016 @ 12:55

Haochuan's attempts at forming crystals of HM 3-2 were successful. The structure was detemined by Peter Turner of the X-ray Crystal Structure Facility in the School of Chemistry, University of Sydney, and forwarded to the group by email on Sept 1st 2016. Files appended.

HM 3-2

 

3-bromo-5-chloro-[1,2,4]triazolo[4,3-a]pyrazine

BrC1=NN=C2C=NC=C(Cl)N21

InChI=1S/C5H2BrClN4/c6-5-10-9-4-2-8-1-3(7)11(4)5/h1-2H

UGKMQVWBWSZEBB-UHFFFAOYSA-N

Synthesis of 3-bromo-5-chloro-[1,2,4]triazolo[4,3-a]pyrazine (HM 3-2)

Crystallizing HM 3-2

Attached Files