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25th September 2012 @ 01:54
This experiment serves two purposes: Two synthesise more of the intended product of this reaction, and to see if lesser levels of fragmentation result at lower temperatures.

Conclusion: Title compound synthesised (21 %).

2536.png


4-(Thieno[3,2-d]pyrimidin-4-yl)morpholine (134 mg, 0.60 mmol, 1 equiv.) was dissolved in dried THF (10 mL) and stirred under argon at -78 °C for 10 min. n-Butyllithium solution (2.5 M, 0.40 mL, 0.6 mmol, 1 equiv.) was added at this temperature dropwise. The stirring solution turned a bright orange colour upon addition of the butyllithium reagent. The solution was stirred at -78 °C for 15 min before elemental iodine (189.7 mg, 0.74 mmol, 1.2 equiv.) in dried THF (10 mL) was added dropwise. The colour of the iodine solution abated upon addition of the first 8 mL iodine solution. This solution was stirred at -78 °C for 1 hr before being allowed to warm to rt.

Post workup yield = 168 mg. Purified via flash chromatography. Two fractions collected.

40% EtoAc/hexane: 71 mg (21%)
5% MeOH/DCM:

HNMR:
JRC18-4NMRFAC.pdf
Attached Files
24th September 2012 @ 04:52
This experiment aims to protect the sulfonamide, which I suspect is interfering in a Suzuki coupling, with a Boc group using Boc2O.

Lit: Neustadt (tet. lett.)
Conclusion: Desired product synthesised (40%).

Experiment start time: 2 pm (24/09/2012)
3-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan- 2-yl)benzenesulfonamide (141.5 mg, 0.500 mmol, 1 equiv.) and Di-tert-butyl dicarbonate (103.1 mg, 0.472 mmol, 0.9 equiv.), DMAP (10.0 mg, 0.08 mmol, 16 mol %) and dried triethylamine (0.08 mL, 0.57 mmol, 1.1 equiv.) were stirred in dried dichloromethane (10 mL) for 24 hr. The reaction mixture was extracted with ethyl acetate (50 mL) and water (50 mL). The organic layer was washed with water (2 x 30 mL) and brine (20 mL) before being dried over anhydrous magnesium sulfate. The residue was concentrated in vacuo to yield a colourless, viscous oil (119 mg). This residue was purified via flash chromatography using 100% EtOAc increasing to 10% MeOH/DCM as the eluent. Three fractions were eluted.

f1: 48 mg
f2: 29 mg
f3: 57 mg

Fractions 1 and 2 contained the desired product (77.0 mg, 0.20 mmol, 40%) as shown by 2D NMR.
46-1NMRFAC.pdf
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21st September 2012 @ 07:15
yield=30.9 mg
19th September 2012 @ 07:24
The Suzuki reactions performed thus far are not giving the desired products. This reaction attempts to reverse the reactivity of the reagents used in the Suzuki reactions. In this case, this is acheived by converting the aryl halide into the boronic ester. This will then in turn be reacted with the starting material from JRC 29-1: An aryl halide.

3241.png


Experiment start time: 4pm, 19/09/2012
MARKED AS EXPERIMENT A

1,4-Dioxane (6 mL) and water (4 mL) were degassed with nitrogen for 4 hr before 4-chloro-6-bromothieno[3,2-d]pyrimidine (105.2 mg, 0.421 mmol, 1 equiv.), bis(pinacolato)diboron (105.3 mg, 0.414 mmol, 0.98 equiv.), potassium acetate (197.7 mg, 2.014 mmol, 4.8 equiv.) and 1,1'-Bis(diphenylphosphino)ferrocene-palladium(II)dichloride (29 mg, 9 mol %) were heated to reflux under a blanket of argon for...

yield=21 mg

Risk Assessment:
As for JRC 32-1, JRC 22-1, JRC 26-1, JRC 36-1, JRC 27-2
Attached Files
19th September 2012 @ 07:23
This experiment is a last ditch effort to synthesise the desired product of the Suzuki reactions I've been performing. Here, a different catalyst is used. A slightly different substrate is also used. It is hoped that the bromine will selectively react with the boronic ester nucleophile in the Suzuki coupling.

3243.png


Experiment start time: 4pm, 19/09/2012
MARKED AS EXPERIMENT B

1,4-Dioxane (6 mL) and water (4 mL) were degassed with nitrogen for 4 hr before 4-chloro-6-bromothieno[3,2-d]pyrimidine (142 mg, 0.57 mmol, 1 equiv.), cesium fluoride (399 mg, 2.62 mmol, 4.6 equiv.), sodium bicarbonate (200 mg, 2.38 mmol, 4.1 equiv.), 4-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)benzenesulfonamide (101.5 mg, 0.358 mmol, 0.7 equiv.) and 1,1'-Bis(diphenylphosphino)ferrocene-palladium(II)dichloride (36 mg, 9 mol %) were added. The resultant red solution was heated to reflux under a blanket of argon for...

yield=6 mg

Risk Assessment:
As for JRC 32-1, JRC 22-1, JRC 26-1, JRC 36-1, JRC 27-2
Attached Files