All Notebooks | Help | Support | About
Templates
Risk Assessment
Archives
Authors
Sections
Yield
Reagent
Mnr
Aew
Ester Synthesis
  • 1 (1)
Tools
Show/Hide Keys
16th November 2012 @ 03:58
Mnr: MNR51-60
Hydrolysis of AEW7-2 to give MNR57-1

See - Synthesis on AEW7-2

MNR57_scheme.png
MNR57-1_table.PNG

Hazard Assessment
HIRAC MNR50.pdf


Procedure

reaction on at 1230pm 16/11/12

NaOH (25.1 g, 628 mmol) was added to a solution of AEW7-2 (62.8 mmol) in EtOH (200 mL) and water (100 mL) and then heated to reflux for 3 hours. The reaction was allowed to cool to room temperature and was then cooled in an ice bath and then acidified to pH 1 using conc. HCl. The brown precipitate was then filtered and rinsed with water to give a crude (wet) off light brown solid. The crude was then recrystallised in Et2O (250 ml) and left to stand overnight. The fine crystals were filtered and washed with Et2O and dried under vacuum (0.802 g). The filtrate was combined with the original washings and concentrated to remove most of the organics and was left in the fridge over night. This was filtered and the dark brown solid was recrystallised in acetone (very messy work up). Again the washing were concentrated as mass recovery was very poor. The above was repeated and a 3rd filter was obtained but as a darker solid as the previous two.

1st filter - 0.802 g, 3.43 mmol, 5%
2nd filter - 4.376 g, 18.7 mmol, 30%
3rd filter - 2.189 g, 9.39 mmol, 15%

Total recovered from filtration - 7.367 g, 31.6 mmol, 50%

The remaining washings were then concentrated and passed through a short column of silica 50-100% EtOAc/Hex

Fracs 1-5 - still to be NMR'd
Fracs 6-17 - still to be NMR'd

NMR
mnr57-1_1st_filter_1H.pdf
mnr57-1_1st_filter_13C.pdf
mnr57-1_1st_filter_19F.pdf
mnr57-1_1st_filter.zip


2nd filter
mnr57-1_2nd_filter_1H.pdf
Linked Posts
This post is linked by:
Attached Files
5th November 2012 @ 00:26
Mnr: MNR51-60
EDC Coupling of MNR51 with Ammonium Hydroxide to give MNR54-1

See - Synthesis of AEW16-1
- Synthesis of MNR52-1
- Synthesis of MNR53-1

MNR54_scheme.png
MNR54-1_table.PNG

Hazard Assessment
HIRAC MNR54.pdf


Procedure

reaction on at 1120am 5/11/12

EDCI (0.080, 0.41 mmol) and HOBt (0.005 g, 0.03 mmol) were added to a solution of MNR51-1 (100 mg, 0.35 mmol) in DCM (5 mL) and the mixture was stirred for 20 minutes. Ammonium hydroxide(28%, 0.04 mL, 0.52 mmol) was added and the reaction mixture stirred at room temperature. After stirring overnight the TLC still showed signs of starting material but it was decided to work the reaction up. It was quenched with sodium bicarbonate (10 mL) and extracted with DCM (3 x 10 mL), dried over MgSO4, filtered and concentrated to give a brown oil (0.105 g)

TLC in 100% EtOAc
MNR54-1_rxn.JPG


Column 80-100% EtOAc/Hexance

Fracs 44-60 as a red oil - first NMR showed mainly product but with traces of EtOAc.

mnr54-1_frac44-60_1H.pdf
mnr54-1_frac44-60_13C.pdf


After another 5 hours on the hivac - 0.034 g, 0.118 mmol, 34%

NMR
mnr54-1_frac44-60_hivac_1H.pdf
mnr54-1_frac44-60_hivac_13C.pdf
mnr54-1_hivac.zip

mnr54-1_frac44-60_19F.pdf
mnr54-1_rerun.zip
Linked Posts
This post is linked by:
Attached Files
2nd November 2012 @ 22:26
Mnr: MNR51-60
EDC Coupling of MNR51 with methylamine to give MNR53-1

See - Synthesis of AEW16-1
- Synthesis of MNR52-1



MNR53-1_table.PNG

Hazard Assessment
HIRAC MNR53.pdf


Procedure

reaction on at 430pm 6/11/12

EDCI (0.111 g, 0.48 mmol) and HOBt (0.007 g, 0.05 mmol) were added to a solution of MNR51-2 (0.140 g, 0.48 mmol) in DCM (7 mL) and the mixture was stirred for 20 minutes. Methylamine in water (35%, 0.5 mL) was added and the reaction mixture stirred at room temperature. After stirring overnight the TLC showed spot to spot conversion. The reaction was quenched with sodium bicarbonate (10 mL) and extracted with with DCM (3 x 10 mL), dried over MgSO4, filtered and concentrated to give a brown oil (0.147 g).

TLC 100% EtOAc
MNR53-1_rxn.JPG


short column, 75-100% EtOAc/Hex

fracs 29-46 0.054 g, as a clear oil which slowly crystallised to give white crystals. 1H NMR showed large water peak. Unsure where this has come from

NMR

mnr53-1_frac29-49_1H.pdf


mnr53-1_conc_1H.pdf

mnr53-1_conc_13C.pdf
mnr53-1_conc_19F.pdf
mnr53-1_conc.zip
Linked Posts
This post is linked by:
Attached Files
1st November 2012 @ 00:11
Mnr: MNR51-60
EDC Coupling of MNR51 with Dimethylamine to give MNR52-1

See - Synthesis of AEW16-1

MNR52_scheme.png
mnr52-1_table.PNG

Hazard Assessment
HIRAC MNR52.pdf


Procedure

reaction on at 1045am 1/1/12

EDCI (0.083, 0.44 mmol) and HOBt (0.005 g, 0.04 mmol) were added to a solution of MNR51-1 (105 mg, 0.36 mmol) in DCM (5 mL) and the mixture was stirred for 20 minutes. Dimethylamine (~5.6 M in absolute ethanol, 0.097 mL, 0.54 mmol) was added and the reaction mixture stirred at room temperature. After 5 hours the reaction looked complete by TLC and it was quenched with sodium bicarbonate (10 mL) and extracted with DCM (3 x 10 mL), dried over MgSO4, filtered and concentrated to give a brown oil (0.075 g)

TLC post workup in 100% EtOAc - traces of starting material
SANY0014.JPG


33.452g

Column 50-75% EtOAc/Hex

Fracs 47-65 - 0.035 g, 0.111 mmol, 30% yield as an orange oil.

NMR
mnr52-1_frac47-65_1H.pdf
mnr52-1_frac47-65_13C.pdf
mnr52-1_frac47-65_conc.zip
mnr52-1_frac47-65_19F.pdf
mnr52-1_frac47-65.zip


reaction closed - 5/11/12 MNR
Linked Posts
This post is linked by:
Attached Files
30th October 2012 @ 21:28
Mnr: MNR51-60
Friedels-Craft Acylation of AEW1-1 to give MNR51-2. Repeating the conditions of MNR51-1 but with a longer reaction time.

See - Synthesis of AEW1-1
- Synthesis of MNR51-1

MNR51_scheme.png
mnr51-2_table.PNG

Hazard Assessment
HIRAC MNR51.pdf


Procedure

reaction on at 7pm 30/10/12
off at 5pm 1/11/12

AlCl3 (2.26 g, 16.9 mmol) was added to a solution of succinic anhydride (0.931 g, 9.30 mmol) and AEW1-1 (1.60 g, 8.46 mmol) in DCM (40 mL). The reaction mixture was stirred at room temperature for 46 hours by which time it had become very thick with possible precipitate. The mixture was concentrated then water (10 mL) was added and the mixture cooled to 0°C and acidified with HCl (37%, 5 mL). The mixture was allowed to warm to room temperature and stirred for 30 min. Again, no solid crashed out, only a red insoluble oil formed. EtOAc (25 ml) was added and the organic laer extracted. The aq layer was then extract with EtOAc (3 x 25 mL), the organics were then combined, dried of magnesium sulphate, filtered and concentrated to give the crude as a red solid.

Crude TLC vs MNR51-1 50% EtOAc/Hex
SANY0015.JPG


Column 40-50% EtOAc/hex

frac 7-24 original nmr still had DCM and MeOH - left on hi-vac overnight

after overnight on the hivac - 1.156 g

mnr51-2_frac7-24_1H.pdf


Unknown singlet at 3.71 and quartet at 2.67?
Linked Posts
This post is linked by:
Attached Files