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18th February 2014 @ 07:45
626 mg of KAB119.2. Dissovled in 6 mL IPA/6 mL water. Added ~6 mL water to make a slurry. Dissolved with ~6.5 mL IPA. Standing at rt. The mixture formed a semi-solid. Non-crystalline.

Suspect amine wasn't pure. Attempted purification using column chromatography.
14th February 2014 @ 22:39
START: 14/02/14


Hazard and Risk Assessment
As for KAB119-1

14/02/14. Suspended KAB8-18 (4.21 g, 11.5 mmol) in ethanol (23 mL) and HCl (1 M, 115 mL). Heated to reflux from 1500; oil bath approx. 130 °C. Yellowish heterogenous solution.

15/02/14. At 0930, mixture still heterogenous. At 950, additional HCl was added (32%, 1.25 mL, 11 mmol). At 1300, mixture still heterogenous. Added ethanol to homogenise (~20 mL). Clear golden yellow solution. At 1600 TLC (neat ethyl acetate) still showed presence of starting material. At 1900, reduced intensity of SM spot but still present. Allowed to reflux overnight.

16/02/14. At 11:30, TLC showed residual SM (100% ethyl acetate). Mostly suspected product spot on the baseline and stained strongly with KMnO4. Expected orange reaction mixture on completion. Added additional HCl (32%, 2.5 mL, 22 mmol). Suspect "1 M HCl" used at the start wasn't actually 1 M HCl. Just make up a fresh solution in future to make sure!
At 13:00, still has starting material. At 15:00 added added more acid (10 mL conc. HCl).

At 17:00, reaction pretty much complete. Tiny shadow of SM by TLC. Reaction was allowed to cool to rt. Cooled in an ice bath. Adjusted to pH ~13 with KOH pellets (~20 g). Extracted with dichloromethane (4 × 300 mL). Combined organic fractions were dried over sodium sulfate, concentrated under reduced pressure and dried in vacuo to give a sickly sweet smelling yellow brown solid (2.53 g, 84%).

17/02/14. The H-NMR looked "off." Suspect salt. Could also see aromatic peaks suggestive of benzoic acid.

18/02/14. Dissolved/suspended solid in water (~40 mL). Basified using NaHCO3 (to pH 10). Extracted with dichloromethane (3 × 60 mL). Combined organics, dried over Na2SO4. Conc under reduced pressure to give a fluffy/powdery yellow solid (2.1 g, 70%).
Attached Files
14th February 2014 @ 22:37

START: 13/02/14 FINISH: 14/02/14

Scheme Hazard and Risk Assessment


ProcedureDissolved MNR10-2 (6.14 g, 13.4 mmol, 1 equiv.) in toluene (500 mL). Started heating to reflux. At about 70 °C methanesulfonic acid (1.40 mL, 21.4 mmol, 1.6 equiv.). Heated to reflux; oil bath at about ~130 °C. Allowed to cool 40 min later. TLC (75% EtOAc/hexanes) indicated complete consumption of SM (KMnO4 stain) No apparent enamide present. Reaction allowed to cool. Worked up according to MNR10.

Crude yield: 5.4 g.

Purified using column chromatography: 50 to 70 to 100% ethyl acetate/hexanes. Product obtained as an off-white foam 4.43 g, 90%.

~400 mg was saved. The remainder of the material was taken on to the next step (i.e. KAB119-2)


Attached Files
2nd February 2014 @ 22:25
START: 31/01/14


Hazard and Risk Assessment

Previous Experiments
Synthesis of (-)-Dibenzoyl-L-tartaric acid (MNR6-1)
Hydrolysis of KAB8-17 (to give KAB119-1)

Data Table

31/01/14. Amounts used are described in the table above. The mixtures of KAB119-1 and MNR6-1 were suspended in IPA and water (with heat gun heating). If relevant, the additional solvent was added. The vials were sealed and stored in the dark at rt over the weekend.
Samples 31/01/14

03/02/14. No crystals formed. The mixtures were concentrated under reduced pressure. Second attempt: X.

Vial 2 was dissolved in 1:1, water:IPA, v/v (4 mL) and allowed to stand at rt. The clear yellow mixture turned into a gel. Water (4 mL) was added. The mixture was sonicated until a heterogenous yellow suspension. Isopropanol was added slowly. Sealed vial. The clear yellow solution at rt overnight.

Vial 2 = crystals
Combined remainder. Dried in vacuo. Total X g.
NOTES: IPA = 2-propanol
Attached Files
28th January 2014 @ 22:28
Reaction proceeded as expected. Product was obtained in 87% yield.

START: 28/01/14
FINISH: 31/01/14


Hazard and Risk Assessment
HNMR KAB119-1 300 MHz CDCl3

28/01/14. Suspended KAB8-17 in ethanol and HCl (1 M). Heated to reflux from 1500; oil bath approx. 130 ° C. Yellowish heterogenous solution.

29/01/14. 0800, clear mixture homogenous and orange. Allowed to cool. Basified to pH 11-13 using solid KOH (about 4 g). Extracted with dichloromethane (2 × 100 mL) and ethyl acetate (100 mL). Combined organic fractions were dried with Na2SO4, concetrated under reduced pressure and dried in vacuo to give an orange solid (1.49 g, 87%)

HNMR consistent with the expected product. No purification required.

Raw HNMR KAB119-1 300 MHz CDCl3
HNMR KAB119-1 300 MHz CDCl3

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Attached Files