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8th May 2013 @ 06:39
Mnr: 21-30
Resolution of MNR26-7 with (-)-dibenzoyl-L-tartaric acid (MNR6-1) to obtain MNR27-26

Starting material from
Hydrolysis of MNR11-18 to give MNR26-7
Synthesis of (-)-Dibenzoyl-L-tartaric acid (MNR6-1)

MNR27-1%20scheme.png



Hazard and Risk Assessment:
As for MNR2-1

MNR26-7 (0.030 g, 0.11 mmol) and (-)-dibenzoyl-L-tartaric acid. 2IPA (0.05 g, 0.11 mmol) was dissolved in a isopropanol (2.5 mL).

MNR27-27 - nothing else added
MNR27-28 - water (0.5 mL) sdded
MNR27-29 - water (0.25 mL) added

The reagents went into solution with minimal heating and we left to stand, sealed, at room temperature overnight.
23rd April 2013 @ 07:48
Mnr: 21-30
Resolution of MNR26-7 with (-)-dibenzoyl-L-tartaric acid (MNR6-1) to obtain MNR27-26

Starting material from
Hydrolysis of MNR11-18 to give MNR26-7
Synthesis of (-)-Dibenzoyl-L-tartaric acid (MNR6-1)

MNR27-1%20scheme.png



Hazard and Risk Assessment:
As for MNR2-1

MNR26-7 (0.10 g, 0.39 mmol) and (-)-dibenzoyl-L-tartaric acid. 2IPA (0.148 g, 0.39 mmol) was dissolved in a mixture of isopropanol (1.6 mL) and water (0.2 mL). The reagents went into solution with minimal heating and we left to stand at room temperature overnight. No crystals appeared overnight for the mixture was transferred to the freezer,the mixture became a gel so IPA (1mL) was added and the mixture was left to stand overnight. No crystals formed - the reaction was not taken any further.
24th October 2012 @ 22:45
Mnr: 21-30
MNR26-1%20scheme.png
mnr26-6.PNG

Hazard and Risk Assessment:
HIRAC MNR7.pdf


Procedure:
MNR12 (3.35 g, 9.14 mmol) (MNR12 as an off white solid found in vial, 1H NMR was clean) was dissolved in a mixture of EtOH (20 mL) and 1M HCl (90 mL and heated to reflux for 14 h.

The solution was allowed to cool to room temperature then cooled in an ice bath, basified with NaOH pellet to pH 12-13 and extracted with DCM (). The organic fractions were combined, dried over magnesium sulphate, filtered and concentrated under reduced pressure to give a dark red/brown solid.

NMR
MNR12-8 starting material-no record of making 12-8, I think the vial was labelled wrong
mnr12-8_vial.zip
Attached Files
5th June 2012 @ 10:47
Mnr: 21-30
Test reaction to see if crude MNR11-16 can be hydrolysed cleanly to MNR26-4

MNR26-4%20scheme.png
mnr26-4%20table.PNG

Hazard and Risk Assessment:
HIRAC MNR7.pdf


Procedure:
MNR11-16 ( 0.40 g, 1.07 mmol) was dissolved in a mixture of EtOH (2 mL) and 1M HCl (10 mL) and heated to reflux for 14 h. The solution was allowed to cool to room temperature then cooled in an ice bath, basified with NaOH to pH 8 and extracted with EtOAc (3 x 20 mL). The organic fractions were combined, dried over magnesium sulphate, filtered and concentrated under reduced pressure to give an orange oil (0.167 g). The aqueous layer was then pH adjusted to pH14 and extracted again with EtOAc (2 x 20 mL). he organic fractions were combined, dried over magnesium sulphate, filtered and concentrated under reduced pressure to give an orange oil (0.028 g).

Total mass recovered - 0.195 g, 69 % -cyclohexyl impurities

mnr26-4_pH8.pdf
mnr26-4_pH14.pdf


Crude 1H NMRS of both fractions showed mainly product with some cyclohexyl-like side product. The fractions were combined and attempts to recrystallise using toluene and hexane were attempted.

1 - toluene (1 pipette), heat to dissolve the contents then hexane (1 pipette) added. white precipitate crashed out immediately so toluene (1pipette) was added and the the mixture heated again to get everything back into solution. Mixture left in the freezer for XX hours.

Characterisation

mnr26-4_pH8.pdf
mnr26-4_pH8.zip


1H NMR (300 MHz, CDCl3): d = 6.64 (s, 1H), 6.59 (s, 1H), 4.96-4.86 (m, NH), 4.74 (dd, J = 9.9, 4.3 Hz, 1H), 3.87 (s, 3H), 3.86 (s, 3H), 3.75-3.49 (m, 2H), 3.05-2.59 (m, 6H).

mnr26-1_1H.pdf
mnr26-1.zip


1H NMR (500 MHz, DMSO): d = 7.00 (s, 1H), 6.92 (s, 1H), 4.93-4.81 (m, 2H), 3.93 (s, 3H), 3.92 (s, 3H), 3.62-3.39 (m, 3H), 2.93-2.78 (m, 3H), 2.71 (t, J = 11.5 Hz, 1H)

Lit m.p. 137.1 to 137.88 C Tang, H., C.-h. Zheng, et al. (2010). "Design and Synthesis of Novel Pyrazino[2,1-a]isoquinolin Derivatives with Potent Antifungal Activity." Archiv der Pharmazie 343(6): 360-366.
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15th March 2012 @ 04:53
Mnr: 21-30

Hazard and Risk Assessment:

As for MNR1-1

MNR28-3

To a cooled solution of MNR27-1 (0.1 g, 0.38 mmol) in DCM (2 mL) at 0°C was added triethylamine (0.0.8 mL, 0.57 mmol) and cyclohexanecarbonyl chloride (0.06 mL, 0.42 mmol). The solution was stirred overnight at room temperature.

The solution was quenched with water (2 mL) and stirred for a further 30 min. The layers were separated and the organic layer was washed with saturated sodium carbonate solution (5 mL), 0.5 M HCl (5 mL) and brine (5 mL). Dried over magnesium sulfate, filtered and concentrated under reduced pressure to give the crude as an orange oil (0.176 g)

Column:- 50-100 EtOAc/PetEther

Fracs 17-26 - 0.063 g, 0.169 mmol, 44% yield (fraction 21 spilt, one of the major fractions)

Characterisation

mnr28-3_1H.pdf
mnr28-3_col.zip

As a 50:50 mixture of rotamers. Peaks not fully resolved at 300 K

1H NMR (300 MHz, CDCl3): d = 6.73 (s, 1H), 6.65 (s, 1H), 5.17-5.005 (m, 1H), 4.91-4.79 (m, 1H), 4.78-4.67 (m, 1H), 4.50 (s, 0.5H), 4.44 (s, 0.5H), 4.17-4.02 (m, 1H), 3.87 (s, 6H), 3.00-2.63 (m, 4H) 2.48 (t, J = 11.1 Hz, 1H), 1.93-1.20 (m, 10H).

mnr28-3_13C.pdf
mnr28-3_col.zip

13C NMR (75 MHz, CDCl3): d =174.8, 164.3, 148.3, 148.1, 126.9, 124.4, 111.7, 108.1, 56.1, 55.9, 54.8, 49.0, 45.3, 40.7, 39.1, 29.2, 29.0, 28.2, 25.7.

Chiral HPLC

KAB1-2.pdf

 

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