All Notebooks | Help | Support | About
11th October 2012 @ 02:49
Product obtained according to 1H NMR evidence. Low yield due to inefficient extraction and losses on DMSO NMR samples. Further characterisation data to be collected.


Synthesis des-methyl pyrazole analogue of TCMDC-123812 using method developed by Alice Williamson.


Reaction Start Time: 15.55 11/10/12
PMY 65-1 (83 mg, 0.35 mmol, 1 equiv.)[calculation error: should be 0.40 mmol] was dissolved in DMF (2 mL) at room temperature. 2-Bromoacetamide (59 mg, 0.43 mmol, 1.2[1.1] equiv.) was added followed by potassium carbonate (98 mg, 0.71 mmol, 2[1.8] equiv.). TLC at 40 mins shows SM and potential product under DMF peak. Not conclusive from initial TLC. Reaction stirred overnight. Partionioned with water and EtOAc (10 mL 1:1). Extracted with EtOAc (3 × 10 mL). Combined organic layers were washed with water (2 × 10 mL), brine and dried (MgSO4) concentrated under reduced pressure and high vacuum to a white solid (36 mg). Crude 1H NMR consistent with expected product and unreacted 2-bromoacetamide (approx 1.1:1 product:acetamide). Aqueous/DMF layer re-extracted using DCM (4 × 10 mL).

Solid recrystallised from hot methanol (approx 4 mL) to obtain colourless needles (10 mg, 9% yield after losses from DMSO NMR samples and recryst). 1H NMR consistent with expected product, clean except very minor impurity doublet at 3.17 ppm. LC/MS shows clean product (264 [M+H]+)

Mpt. 220-221 °C (MeOH)

1H NMR crude
1H NMR recrystallised

Sample submitted for service NMR.

TLC (10% MeOH/DCM) visualised with UV and vanillin:
TLC 40 min

LC/MS after recryst

0to100ov30 MNR method

See also:
Ester synthesis (AEW 5-3)
Hydrolysis of PMY 64-1 ethyl ester (PMY 65-1)

Risk and Hazard Assessment:
As for: Synthesis of ether-linked analogue of TCMDC-123812 (PMY 37-1) except the safer base, potassium carbonate and dimethylformamide as solvent (flammable, harmful in contact with skin or inhaled, eye irritant, may damage unborn child).
Linked Posts
Attached Files
TLC 40 min
1H NMR crude
1H NMR recrystallised
LC/MS after recryst