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2nd October 2012 @ 05:04
Desired product obtained in 35% yield according the 1H NMR. Progressed to cyclodehydration.

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Coupling of pyrrole acid chloride and L-serinamide for conversion to the oxazoline and oxazole product.

PMY61-1.png

Reaction Start Time: 13.00 02/10/12
JRC 2-1 (250 mg, 1.07 mmol, 1 equiv.) was stirred in PhMe (2 mL). Thionyl chloride (0.16 mL, 2.14 mmol, 2 equiv.) was added and the mixture stirred at room temperature. 1 drop DMF added. After 3 hours, the reaction was concentrated under reduced pressure twice from PhMe. Triturated with hexanes (8 mL) and concentrated to a yellow oil [normally a solid, not a promising sign]. Dissolved in THF (2 mL)

L-serinamide.HCl (188 mg, 1.34 mmol, 1.25 equiv.) was stirred in THF (3 mL). DIPEA (0.77 mL, 4.42 mmol, 3.3 equiv) was added. The slurry was stirred at room temperature. The solution of the acid chloride was added to the slurry (rinsed 1 mL THF). Left to stir overnight. After overnight reaction, the mixture was concentrated under reduced pressure. The residue was stirred in saturated NaHCO3 (10 mL) and extracted with DCM (3 × 10 mL). The combined extracts were washed with brine, dried (MgSO4) and concentrated to a yellow solid. Purification by chromatography on silica (1-7% MeOH/DCM) gave mixed spot fraction, PMY 61-1-A and PMY 61-1-B, pure white crystalline solid (119 mg, 35% of theory yield). PMY 61-1-B clean and consistent with expected product by 1H NMR.

PMY 61-1-B mpt 203-205 °C (CH2Cl2/MeOH)

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


NMR:
1H NMR PMY 61-1-B
1H NMR PMY 61-1-A


See Also:
Coupling of pyrazole MJT 3-1 with serinamide (MJT 4-1)
Scaled-up coupling of pyrrole acid chloride and serine methyl ester (PMY 57-2)
Coupling of pyrrole acid chloride and serine methyl ester (PMY 57-1)

Risk and Hazard Assessment:
As for: Synthesis of TCMDC-123812 via acid chloride (PMY 10-6)
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Attached Files
Scheme
1H NMR PMY 61-1-A
1H NMR PMY 61-1-B
TLC overnight