2- Chloro-1 -methyl-pyridinium iodide

To a solution of the acid (300 mg, 1.1 mmol) in CH2CI2 (5 mL) was added 2-chloro-1-methyl-pyridinium iodide (the Mukaiyama reagent, 330 mg, 1.3 mmol) and the aniline (1.29 g, 5.89 mmol). The mixture was heated at reflux for 1 h and then allowed to cool. EtsN (0.30 mL, 2.2 mmol) was added, and the mixture was heated at reflux for an additional 20 h, allowed to cool, poured into water (40 mL), and extracted with CH2CI2 (3 x 20 mL). The combined organic extracts were dried, filtered, and concentrated. The crude material was purified by column chromatography (25% EtOAc in hexanes) to furnish the amide (387 mg, 75%). 

COOH/Pr3N 2 - chloro 1 - methyl-pyridinium iodide... 

Mukaiyama s Reagent (2-Chloro-l-methyl pyridinium Iodide or 2-Fluoro-l-methyl pyridinium p-toulenesulfonate)... 

Mukaiyama reagent such as 2-chloro-l-methyl-pyridinium iodide for esterification or amide formation. 

LACTONIZATION Boron trifluoride etherate. 2-Chloro-l-methyl-pyridinium iodide. 2,2 -Dipyridyl disulfide-Triphenylphosphine. Phosphorus pentoxide-Methanesulfonic acid. Triphenylphosphine-Diethyl azodicarboxylate. 

A route to chiral oxazolidinones reported last year (Vol. 23, p. 272) has been extended to the preparation of chiral p-lactams such as (96), which are potential precursors of carbapenems the oxazolidinones were opened reductively to P-aminoacids and then recyclized using 2-chloro-l-methyl-pyridinium iodide.72... 

Scheme 6. Reagents and conditions a) N2H4, EtOH, 100°C, 87% b) RCOOH (3eq), 2-chloro-l-methyl pyridinium iodide, EtsN, CH3CN, 25 °C, 73% c) PPTS, EtOH, 25 °C then AC2O, EtsN, DMAP (cat), CH2CI2, 25 °C, 72% d) TBAF, THE then MejNSOj, Pyr. 25 °C, 85% e) CAN, CH3CN, H2O, 25 X. 30%, f) MeONa, MeOH, 25 °C, 75%.

Chloro-l-methylpyridinium iodide (1) reacts with a mixture of a carboxylic acid and an alcohol, in the presence of two equivalents of base, to form an ester (eq 1). The pyridinium salt (2) is formed rapidly by displacement of chloride from (1) by the carboxylate subsequent reaction with the alcohol results in formation of the ester, along with 1 -methyl-2-pyridone (3). A variety of solvents may be employed, but yields are highest in dichloromethane or pyridine. Tri-n-butylamine or Triethylanune are often used as base. The co-product (3) is insoluble in dichloromethane and so precipitates from this solvent. Good results are obtained even for hindered carboxylic acids and alcohols. 

Mukaiyama and coworkers [24] found that 2-chloro-3-methoxymethyl-l-me-tbylpyridinium iodide is also suitable for effecting macrolactonization. Furthermore [25], the cyclization mediated by the 2-chloropyridinium salts described above sometimes gives no satisfactory yields. It is mainly due to the decomposition of the pyridinium salts under the cyclization conditions by the attack of triethylamine to either the 1-methyl group or the 2-position of the pyridinium ring to form 2-chloropyridine or 2-ammoniopyridinium salts. To solve this... 

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