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21st June 2012 @ 01:46
Mnr: 31-40

Hazard and Risk Assessment:

ProcedureTo a cooled solution of MNR30-7(0.09 g g, 0.34 mmol) in DCM (2 mL) at 0°C was added triethylamine (0.05 mL, 0.51 mmol) and benzoyl chloride (0.05 mL, 0.38 mmol). The solution was stirred for XX hours at room temperature.

(on at 11am 21/6/12)

TLC after 8 hours show slight trace of SM so reaction was left overnight

First TLC plate in 100% EtOAc. mnr38-1, mnr30-7, mnr39-1 Second TLC plate 20% MeOH/EtoAc. mnr30-7, co, mnr39-1, co, mnr12-1

SANY0200.JPG

In the morning, the reaction was quenched with water (3 mL) and stirred for 30 minutes then the organic layer was separated and washed with sodium carbonate solution (5 mL), 1M HCl (5 ml) and brine (5 mL), dried and filtered to give the crude as an orange oil (0.156 g)

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

Fracs 38-60 0.046 g as a white solid - original nmr contained EtOAc but after taking the product up in DCM and putting under the high vac the product was recovered as a clean white solid

NMR

mnr39-1_1H.pdf
mnr39-1_frac38-60.zip

1H NMR (500 MHz, CDCl3): d = 7.49-7.39 (m, 5H), 6.78 (br, 1H), 6.62 (s, 1H), 5.17 (br, 1H), 4.95-4.75 (m, 2H), 4.33 (br, 1H), 4.14-4.02 (m, 1H), 3.84 (br, 6H), 3.03 (br, 1H), 2.95-2.73 (m, 2H), 2.73-2.59 (m, 1H).

mnr39-1_13C.pdf
mnr39-1_13C_zoom.pdf
mnr39-1_frac38-60.zip

13C NMR (125 MHz, CDCl3): d = 170.3, 164.2, 148.4, 148.1, 134.2, 130.7, 128.7, 127.4, 127.1, 124.4, 111.8, 108.2, 56.2, 55.9, 54.5, 51.4, 46.1, 39.1, 28.3.

Chiral HPLC- 99% ee using the CHIRALCEL OD-H column, 25% EtOH:Hex with 0.1% TEA and a flow rate of 0.75 mL/min

mnr39-1_25EtOH_075ml_23June.pdf

melting point - 104-106 °C

IR 

1d S IR MNR39-1 dont include.jpg
Attached Files
21st June 2012 @ 01:36
Mnr: 31-40

Hazard and Risk Assessment: As for MNR1-1

ProcedureTo a cooled solution of MNR30-7(0.10 g g, 0.38 mmol) in DCM (2 mL) at 0°C was added triethylamine (0.06 mL, 0.57 mmol) and cyclohexanecarbonyl chloride (0.06 mL, 0.42 mmol). The solution was stirred for a total of 22 hours at room temperature.

(on at 11am 21/6/12)

In the morning, the reaction was quenched with water (3 mL) and stirred for 30 minutes then the organic layer was separated and washed with sodium carbonate solution (5 mL), 1M HCl (5 ml) and brine (5 mL), dried and filtered to give the crude as an orange oil (0.165 g)

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

Fracs 35-51 0.053 g as a white solid - original nmr contained EtOAc but after taking the product up in DCM and putting under the high vac the product was recovered as a clean white solid

NMR

mnr38-1_1H.pdf
mnr38-1_frac35-51.zip

1H NMR (500 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).

mnr38-1_13C.pdf
mnr38-1_frac35-51.zip

13C NMR (125 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, 25.6.

Chiral HPLC - 99% ee using the CHIRALCEL OD-H column, 25% EtOH:Hex with 0.1% TEA and a flow rate of 0.5 mL/min

mnr38-1_25EtOH_05ml_24June.pdf

IR 

1b S IR MNR38-1.jpg
Attached Files
21st June 2012 @ 00:27
Resolution of MNR26-5 with (+)-dibenzoyl-D-tartaric acid (MNR5-1)

MNR30-1%20scheme.png

Hazard and Risk Assessment:
As for MNR2-1

Procedure
MNR26-5 (EtOAc wash fraction) (1.10 g, 4.19 mmol) and MNR5-1 (1.62 g, 4.19 mmol) was dissolved in IPA (10 mL) and water (2 mL) with heating. All the reagents went into solution and the mixture was left to stand. After 3 hours everything remained in solution so the flask was transferred to the freezer. After 1 hour the solution had frozen so the flask was allowed to reach room temperature again by which time it turned back into a solution. The flask was then stored in the fridge over the weekend by which time white lumpy crystals had formed. These were filtered and washed with IPA:Water (8:1) then hexane and dried to give a white solid 0.908 g, 1.46 mmol, 70%
Test workup
salt (0.036 g, 0.058 mmol) was treated with sodium carbonate solution (5 mL) and extracted with EtOAc (20 ml x 5). The organic fractions were dried, filtered and concentrated to give a clear oil 0.014 g, 0.053 mmol, 91 %)
HPLC showed 75% ee
The remaining salt was dissolved in IPA (18 mL) and water (3 mL) and stored in the fridge overnight. The white solid was filtered and washed with IPA and hexane to recover 100% of what was used therefore no further improvement on the ee. The solid was redissolved in IPA (30 mL) and water (3ml) with heating and allowed to stand.

Conical flask found in the freezer (15/10/12) wih nice white crystals in solution. Filtered and washed with Et2O and dried under vacuum.

Vial tare - 16.131 g
21st June 2012 @ 00:25
Resolution of MNR26-1 with (+)-dibenzoyl-D-tartaric acid (MNR5-1)

MNR30-1%20scheme.png

Hazard and Risk Assessment:
As for MNR2-1

MNR26-5 (MeOH wash fraction) (1.63 g, 6.21 mmol) and MNR5-1 (2.39 g, 6.21 mmol) was dissolved in IPA (13 mL) and water (3 mL) with heating. All the reagents went into solution and the mixture was left to stand and within 15 minutes the mixture was solid. IPA (1mL) was added and with heating the solid broke down into small enough lumps to be filtered. The solid was washed with IPA:water (4:1) and dried to give an off white solid (2.969 g)
The solid was then mixed with IPA (17 mL) and water (3 mL) and heated to reflux. The mixture did not become a solution so IPA (5 mL) and water (2 mL) was added in portions until the refluxing mixture became a solution.

Allowed to cool to room temperature and left in fridge over the weekend. An off white solid had crashed out and was washed with IPA/hexane and dired under vacuum.

Taken to pH 14
Extract EtOAc
Nothing, total crap, just traces

** Reaction not taken any further
20th June 2012 @ 02:11
Resolution of MNR26-5 with (+)-dibenzoyl-D-tartaric acid (MNR5-1)

MNR30-1%20scheme.png

Hazard and Risk Assessment:
As for MNR2-1

Procedure
MNR26-5 (EtOAc extraction minus oil that had crashed out) (1.82 g, 6.94 mmol) and MNR5-1 (2.67 g, 6.94 mmol) was dissolved in IPA (15 mL) and water (3 mL) with heating. All the reagents went into solution and the mixture was left to stand. After standing overnight at room temperature the solution has formed a solid gel. IPA (15 mL) was added and the flask stored in the fridge for 2 hours then at room temperature overnight. The solid was filtered and washed with IPA and hexane to give a just off white solid (1.667 g). The solid was redissolved in IPA (25mL) and water (3 mL) and left to stand at room temperature for 3 hours, solid filtered and washed with hexane. Dissolved in sodium carbonate solution and extracted with EtOAc (25 mL x 3), dired, filtered and concentrated to give a sticky white solid (0.171 g, 0.65 mmol, 9 %)

1H NMR
mnr30-7_1H.pdf

13C NMR
mnr30-7_13C.pdf

Chiral HPLC - 99% ee using the CHIRALCEL OD-H column and a flow rate of 0.5 mL/min
mnr30-7_scaleup.pdf

Chiral HPLC of racemic MNR26-1 using the CHIRALCEL OD-H column and a flow rate of 0.5 mL/min. Peaks at 41 and 44 mins
mnr26-1 15EtOH 05mL_120412.pdf
Attached Files