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21st June 2012 @ 01:21
MNR14-4%20scheme.png

Hazard and Risk Assessment:
As for MNR12-2

Procedure
MNR22-2 (frac 4-7) (9.0 g, 22.6 mmol) was stirred with methanesulfonic acid (73 mL, 1.1 mol) at room temperature and after 2 hours all the starting material had been consumed. The reaction was quenched with saturated sodium carbonate and extracted with EtOAc (300 mL x3). The organic fractions were dried over magnesium sulfate, filtered and concentrated under reduced pressure.

The crude was then purified by FCC EtOAc/Hexane (50-100%)

Fracs 8-12
7th June 2012 @ 02:24
test reaction of the excess MSA PS reaction on MNR22-2 (frac 4-7)

MNR14-4%20scheme.png

MNR14-4%20table.PNG

Hazard and Risk Assessment:
As for MNR12-2

Procedure
MNR22-2 (frac 4-7) (0.70 g, 1.76 mmol) was stirred with methanesulfonic acid (5.7 mL, 87.8 mmol) at room temperature and after 1 hour all the starting material had been consumed. The reaction was quenched with saturated sodium carbonate and extracted with EtOAc (40 mL x2). The organic fractions were dried over magnesium sulfate, filtered and concentrated under reduced pressure.
Attached Files
5th June 2012 @ 09:59
Scale up of MNR11-16

Synthesis of MNR11-16

MNR11-1%20scheme.png

MNR11-17%20table.PNG

Hazard and Risk Assessment:
HIRAC MNR11.pdf


Procedure:
To a solution of MNR8-5 (8.30 g, 17.87 mmol) in toluene (60 mL) at room temperature was added methanesulfonic acid (2.49 mL, 38.41 mmol) and the mixture was refluxed for 30 minutes. The reaction was quenched with saturated sodium carbonate and extracted with EtOAc (50 mL x 3). The organic fractions were dried over magnesium sulfate, filtered and concentrated under reduced pressure to give the crude as a thick orange oil.

Crude - 7.071 g, 106 % - still contains toluene

mnr11-17_crude.pdf
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5th June 2012 @ 09:51
Mnr: 11-20
test reaction to see if the purity of MNR8-5 is effectiong the PS reaction.

MNR11-1%20scheme.png

MNR11-16%20table.PNG

Hazard and Risk Assessment:
HIRAC MNR11.pdf


Procedure:
To a solution of MNR8-5 (0.6 mg, 1.29 mmol) in toluene (10 mL) at room temperature was added methanesulfonic acid (0.18 mL, 2.77 mmol) and the mixture was refluxed for 30 minutes. The reaction was quenched with saturated sodium carbonate and extracted with EtOAc (20 mL x 3). The organic fractions were dried over magnesium sulfate, filtered and concentrated under reduced pressure.

column chromatography on silica gel (60-100 % EtOAc:hexane) to give MNR11 as an off white solid (0.467 g, 1.25 mmol, 97 %)

mnr11-16_crude.pdf


Characterisation


kab01-2_1H.pdf
kab1-2.zip


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

1H NMR (500 MHz, CDCl3): d = 6.73 (s, 1H), 6.64 (s, 1H), 5.11 (dd, J = 13.3, 2.6 Hz, 1H), 4.90-4.81 (m, 1H), 4.76-4.68 (m, 1H), 4.48 (s, 0.5H), 4.45 (s, 0.5H), 4.10 (s, 0.5), 4.06 (s, 0.5H), 3.87 (s, 3H), 2.98-2.75 (m, 3H), 2.70 (s, 0.5H), 2.67 (s, 0.5H), 2.53-2.43 (m, 1H), 1.91-1.67 (m, 5H), 1.62-1.48 (m, 2H), 1.36-1.22 (m, 3H).

kab01-2_13C.pdf
kab1-2.zip


13C NMR (125 MHz, CDCl3): d = 174.9, 164.4, 148.3, 148.1, 126.9, 124.4, 111.7, 108.1, 56.1, 55.9, 54.8, 49.0, 45.4, 40.8, 39.2, 29.3, 29.0, 28.3, 25.7, 25.7, 25.7

Lit mp 98-100°C - Sadhu, P. S.; Kumar, S. N.; Chandrasekharam, M.; Pica-Mattoccia, L.; Cioli, D.; Rao, V. J. Bioorganic & Medicinal Chemistry Letters 2012, 22, 1103

Lit m.p. 91-92°C - Kim, C. S.; Min, D. Y. Arch. Pharm. Res. 1998, 21, 744

See also

Acid-mediated PS cyclisation to give racemic PZQ (KAB3-3), the dimethoxy N-benzoyl PZQ analogue (KAB8-1), the dimethoxy PZQ analogue (KAB1-2) and the N-benzoyl PZQ analogue (KAB7-1)
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