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17th October 2012 @ 02:34
Product obtained in 62% yield.

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Coupling of pyrrole acid OSM-S-4 and serine methyl ester using EDC/HOBt.

PMY67-1.png

Reaction Start Time: 14.20 17/10/12
Acid OSM-S-4/JRC 2-1 (2.00 g, 8.6 mmol, 1 equiv.) was stirred at room temperature in DCM (60 mL) under nitrogen. Dark solution. HOBt (0.12 g, 0.9 mmol, 0.1 equiv.) and EDC.HCl (1.97 g, 10.3 mmol, 1.2 equiv.) was added followed by DIPEA (3.6 mL, 20.8 mmol, 2.4 equiv.). After 10 minutes, DL-serine (1.47 g, 9.4 mmol, 1.1 equiv.) was added. Mostly in solution, a few clumps. After 40 minutes, the reaction is a solution. TLC at 1 hour shows SM, non-polar impurity [as seen in previous couplings... but not observed in Alice's hydrazine couplings. Maybe because she doesn't use a base?] and new products. After overnight at room temperature NH4Cl was added and the mixture then 1M HCl added until pH 1. The layers were separated and the organic layer washed with water (3 × 20 mL), Na2CO3 (20 mL), water (3 × 20 mL), brine then dried (MgSO4) and concentrated under reduced pressure to a brown foam (2.67 g). Purification by chromatography on silica (2-5% MeOH/DCM) gave tan foam (1.79g, 62% of theory).

TLC (5% MeOH/DCM) visualised with UV and vanillin:
TLC 1 hour


NMR:
1H NMR


See also:
EDC Coupling of Pyrrole Carboxylic acid with Hydrazine Hydrate (AEW 14-2)
Conversion of oxazole carboxylic acid to primary amide (PMY 60-3)
Scaled-up coupling of pyrrole acid chloride and serine methyl ester (PMY 57-2)

Risk and Hazard Assessment:
As for: Synthesis of N-Phenyl analogue of TCMDC-123812 (PMY 23-1)
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Attached Files
Scheme
TLC 1 hour
1H NMR