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2nd September 2014 @ 23:44

Background: Synthesis of the pyridinyl boronic ester as an alternative to the boronic acid which doesn't appear to work. 

GitHub link: #250

Literature ref: 10.1016/j.tet.2003.10.020

Reaction Scheme

Titration of n-BuLi

2.5 M n-BuLi was titrated against N-benzylbenzamide (100 mg portions) according to the following procedure: http://www.scripps.edu/shenvi/Education_files/titration.pdf

The results were: 1) 1.83 M, 2) 2.02 M, 3) 1.03 M, 4) 1.71 M, 5) 1.98 M, 6) 1.71 M. From the results it was assumed that the concentration of n-BuLi was around 1.7 M for the subsequent reactions. 1.03 M is an outlier, likely due to experimental error.

Procedure

Started 

To a solution of ~1.7 M solution of n-BuLi (4.8 mL, 8.2 mmol, 1.2 equiv.) in freshly distilled tetrahydrofuran (40 mL), cooled to -78°C, was added a solution of 2,6-dichloropyridine (1.0 g, 6.8 mmol, 1 equiv.) in THF (20 mL). On addition of the 2,6-dichloropyridine the reaction mixture turned x. The reaction was stirred at -78°C for 45 min. A solution of triethylborate (1.2 g, 1.0 mL, 8.2 mmol, 1.2 equiv.) in THF (8 mL) was added and the x mixture stirred at -78°C for 1 h.

 

HIRAC and Risk Assessment

HIRAC JU 24-1.pdf

For the risk assessment please see JU 20-1

InChI strings

InChI=1S/C5H3Cl2N/c6-4-2-1-3-5(7)8-4/h1-3H

to

InChI=1S/C11H15BClNO2/c1-10(2)11(3,4)16-12(15-10)8-6-5-7-9(13)14-8/h5-7H,1-4H3

SMILES

ClC1=CC=CC(Cl)=N1

to

ClC1=CC=CC(B2OC(C)(C)C(C)(C)O2)=N1 

Attached Files
1st September 2014 @ 00:05

Repeat synthesis of JU 1-20 to validate new conditions. 

Reaction Scheme

Procedure

Started 

2,6-Dichloropyrazine (Aldrich, 1.00 g, 6.8 mmol) was dissolved in ethanol (10 mL) to give a clear solution. Hydrazine hydrate (1.0 mL, 1.0 g, 20.4 mmol, 3 equiv) was added resulting in a pale yellow solution. The resulting mixture was heated at reflux (bath temperature 100˚C) for x h. 

 

HIRAC & Risk Assessment

See JU 1-1

InChI strings

InChI=1S/C4H2Cl2N2/c5-3-1-7-2-4(6)8-3/h1-2H

to

InChI=1S/C4H5ClN4/c5-3-1-7-2-4(8-3)9-6/h1-2H,6H2,(H,8,9)

SMILES

ClC1=CN=CC(Cl)=N1

to

ClC1=CN=CC(NN)=N1

31st August 2014 @ 23:59

Repeat synthesis of JU 1-20 to validate new conditions. 

Reaction Scheme

Procedure

Started 

2,6-Dichloropyrazine (Aldrich, 1.00 g, 6.8 mmol) was dissolved in ethanol (10 mL) to give a clear solution. Hydrazine hydrate (1.0 mL, 1.0 g, 20.4 mmol, 3 equiv) was added resulting in a pale yellow solution. The resulting mixture was heated at reflux (bath temperature 100˚C) for x h. 

 

HIRAC & Risk Assessment

See JU 1-1

InChI strings

InChI=1S/C4H2Cl2N2/c5-3-1-7-2-4(6)8-3/h1-2H

to

InChI=1S/C4H5ClN4/c5-3-1-7-2-4(8-3)9-6/h1-2H,6H2,(H,8,9)

SMILES

ClC1=CN=CC(Cl)=N1

to

ClC1=CN=CC(NN)=N1

30th August 2014 @ 04:01

 Started Friday afternoon (4:30 pm) posted Saturday.

 

Procedure:

AEW 189-1 *purified (500 mg, 4.23 mmol, 1 equiv.) was dissolved in DMF (6 mL) under Ar. Cs2CO3 (1.38 g, 4.23 mmol, 1 equiv.) was added and the reaction mixture was stirred at room temperature for 10 minutes. MeI (0.29 mL, 4.66 mmol, 1.1 equiv.) was then added and the reaction stirred at room temperature overnight (11 am Sat). TLC indicated spot to spot conversion with poduct much lower Rf (unexpected) >0.1 50:50 EtOAc/Hex.

The reaction mixture was diluted with EtOAc (12 mL) and washed with water (5 x 8 mL). Combined aqueous layers were washed with EtOAc (10 mL) and then combined organic layers were washed with brine (6 mL), dried (MgSO4), filtered and evaporated to give

Data:

 

Hazard and Risk Assessment:

See Synthesis of methyl 2-methoxy-2-methylpropanoate (AEW 193-1)

InChi:

InChI=1S/C4H8O3/c1-4(2,7)3(5)6/h7H,1-2H3,(H,5,6)

to

InChI=1S/C6H12O3/c1-6(2,9-4)5(7)8-3/h1-4H3


Smiles:

OC(C)(C)C(O)=O

to

O=C(OC)C(C)(C)OC

29th August 2014 @ 03:14

55-1 scheme

 

TM 52 (pure, 170 mg, 0.393 mmol: Synthesis of (E)-N-(3-chlorophenyl)-6-(2-(4-(trifluoromethoxy)benzylidene)hydrazinyl)pyrazine-2-carboxamide (TM 52-1)) was stirred into DCM (6 mL), PIDA (130 mg, 0.393 mmol, 1 eq) added, and the reaction mixture stirred at rt for ?? h.

 

InChIs:

InChI=1S/C19H13ClF3N5O2/c20-13-2-1-3-14(8-13)26-18(29)16-10-24-11-17(27-16)28-25-9-12-4-6-15(7-5-12)30-19(21,22)23/h1-11H,(H,26,29)(H,27,28)/b25-9+

to

InChI=1S/C19H11ClF3N5O2/c20-12-2-1-3-13(8-12)25-18(29)15-9-24-10-16-26-27-17(28(15)16)11-4-6-14(7-5-11)30-19(21,22)23/h1-10H,(H,25,29)

HIRAC:

HIRAC.pdf

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