TCMDC_ArylPyrrole

 

Mnr: MNR91-100

Attempted Solvent Free, 1-Pot Synthesis of Ether MNR98-2 

Starting material AEW2-2

 Hazard Assessment

Procedure

Methyl bromoacetate (1 mL, 10.2 mmol) was added to a flask with tpye 3A molecular sieve powder and AEW2-2 (0.10 g, 0.46 mmol) was added.  Sodium borohydride (19 mg, 0.51 mmol) was added and the reaction was allowed to stir at room temperature overnight.  TLC in the morning showed no reaction, so it was left.  After 24 hours TLC still showed no reaction and was not taken any further. 

Strings

Starting material

InChI=1S/C13H12FNO/c1-9-7-11(8-16)10(2)15(9)13-5-3-12(14)4-6-13/h3-8H,1-2H3

Product

InChI=1S/C16H18FNO3/c1-11-8-13(9-21-10-16(19)20-3)12(2)18(11)15-6-4-14(17)5-7-15/h4-8H,9-10H2,1-3H3

 

Mnr: MNR91-100

Starting material AEW2-2

Attempted 1-pot synthesis of MNR98-1 in an aportic solvent.

 

 

 Hazard Assessment

Procedure

To a solution of AEW2-2 (0.10 g, 0.46 mmol) in THF (8 mL) at room temperature was added sodium borohydride (19 mg, 0.51 mmol) follwed by methyl bromoacetate (0.07 mL, 0.76 mmol) and the reaction was left to stir overnight (16 hours).  TLC in the morning showed mainly starting material and a new lower running spot, this looked promising but the spot on the slowly stained blue on sitting, characteristically similar to alcohol MNR97-1.  Actone (5 mL) was added the the mixture was left to stir for 5 mniutes then concentrated under vacuum.  Water (5 mL) was then added and extracted with DCM (10 mL x 3).  The organics were combined, dried, filtered and concentated to give a brown solid.  Crude NMR showed only starting material and degraded alcohol.  Reaction not taken any further forward. 

Strings

Starting material

 InChI=1S/C13H12FNO/c1-9-7-11(8-16)10(2)15(9)13-5-3-12(14)4-6-13/h3-8H,1-2H3

Product

InChI=1S/C16H18FNO3/c1-11-8-13(9-21-10-16(19)20-3)12(2)18(11)15-6-4-14(17)5-7-15/h4-8H,9-10H2,1-3H3

 

NMR

*Feb 2015 - Crude NMR was not uploaded at the time and can't be found on the servers. It may have been mislabelled or it may have been run under another user name seeing as it was just a quick crude run.  

Mnr: MNR91-100

Starting material from AEW2-2

Procedure modified from AEW3-2

Hazard Assessment

Procedure

AEW 2-2 (0.200 g, 0.92 mmol) was dissolved in MeOH (15 mL) at room temperature and sodium borohydride (44 mg, 1,15 mmol) was added.  The reaction was stirred for 4 hours at which point TLC only faint traces of starting material so the reaction was worked up due to the time.  Acetone (5 mL) was added and the raction was stirred for a further 10 minutes then it was concentrated under vacuum.  Water (5 mL) was added and extracted with DCM (5 mL x 3), the organics were combined, dried, filtered and concentrated to give a bark brown oil. 

NMR

Starting material

 

The NMR of the crude was far from clean but it showed signs of product.

Crude

 

Same sample after 17 hours at room temperature.

Overlay of the above spectra.

The product has completely decomposed overnight at room temperature 

Conclusion

The alcohol should be taken on straight away due to it's instabilities 

Strings

Starting material

InChI=1S/C13H12FNO/c1-9-7-11(8-16)10(2)15(9)13-5-3-12(14)4-6-13/h3-8H,1-2H3

Product

InChI=1S/C13H14FNO/c1-9-7-11(8-16)10(2)15(9)13-5-3-12(14)4-6-13/h3-7,16H,8H2,1-2H3

Mnr: MNR91-100

As per compound 3a here

 

 Procedure

A mixture of Ethyl 5-hydroxy-2-methylindole-3-carboxylate (1.00 g, 4.56 mmol), iodobenzene (0.36 mL, 3.19 mmol), CuI (0.13 g, 0.68 mmol) and Cs2CO3 (2.08 g, 6.39 mmol), in DMF (7mL) was stirred at 120 °C under argon for 16 h during which time the reaction turned black.  Water (40 mL) was added and was extracted with EtOAc (30 mL x 3) (there was trouble dissolving some of the crude and it was left behind).  The organic fractions were combined and dried over magnesium sulphate, filtered and concentrated to give a browm oil (still containing DMF)

Column - 30-75% EtOAc/Hex

Fracs 5-17 - higher running new spot - brown solid - 0.147 g

Fracs 19-41 - looks like starting material - 0.319 g

 

Strings

Starting Material

InChI=1S/C12H13NO3/c1-3-16-12(15)11-7(2)13-10-5-4-8(14)6-9(10)11/h4-6,13-14H,3H2,1-2H3

InChI=1S/C6H5I/c7-6-4-2-1-3-5-6/h1-5H

Product

InChI=1S/C18H17NO3/c1-3-22-18(21)17-12(2)19(13-7-5-4-6-8-13)16-10-9-14(20)11-15(16)17/h4-11,20H,3H2,1-2H3

Mnr: MNR61-70

Synthesis of N-Substituted Pyrroles Under Catalyst- and Solvent-Free Conditions, Synthetic Communications, Volume 42, Issue 16, 2012




Hazard Assessment


Procedure
MNR66-1 (0.160 g, 0.79 mmol) and 4-fluoroanilne (0.06 mL, 0.67 mmol) were heated at 120˚C for X hours.