L-Proline methyl ester

Figure 56.3 The preparation of Boc-protected L-proline methyl ester.

General procedure for the production of Boc-protected a,a-diaryl-L-prolinols (6). To 100 mL of a 0.42 M solution of ArMgBr in THF (0.042 mol) at 0°C was added N- t- BOC)-L-proline methyl ester (5) (3.0 mL, 0.014 mol) dropwise via syringe over a five-minute period. The solution was stirred for at least 4 h at 25°C and then cooled to 0°C. After slow addition of 3 mL of water, the solution was slowly warmed to ft with stirring. The mixture was decanted and the solid was washed with 100 mL of ethyl ether. The organics were pooled and washed with brine, dried with sodium sulfate and evaporated to yield the final compound. 

Boc-O-benzyl-L-homoserine (Boc = t-butoxicarbonyl) was transformed to L-proline methyl ester, and the benzyl ether was removed by hydrogenolysis. The compound was dissolved in 50% acetic acid in methanol and the reaction mixture was degassed by bubbling nitrogen for 5 minutes then 10% Pd/C was added. The system was evacuated for 5 minutes and then pressured to 45 psi of hydrogen for 48 hours at room temperature.66... 

Bycroft and Lee (75CC988) developed this into a general method for the asymmetric synthesis of a-amino acids, wherein the chiral auxiliary (L-proline) could be recovered and recycled. Condensation of L-proline methyl ester with a-keto acids using DCC, followed by a treatment with anhydrous ammonia at room temperature, gave the 3-hydroxypiperazine-2,5-diones with high stereoselectivity (cf. Scheme 79). These could be... 

Biginelli synthesis of 3,4-dihydropyrimidin-2( 1 //)-oncs (99) from an aldehyde, a /3-diketone, and urea is catalysed by L-proline methyl ester hydrochloride.276 Although evidence strongly supports an enamine mechanism, the products were essentially racemic. 

The treatment AT-carbonyl pyrrolidine derivatives with PhIO/TMSN3 (1 2) leads to a-azidonation of the pyrrolidine ring (Scheme 7) [25]. Similar results were obtained with the piperidine analogs, although product yields were much improved when iodosylbenzene was replaced with o-iodosylbenzoic acid and the reactions were conducted under reflux. Extension of the azidonation methodology to carbonyl derivatives of L-proline methyl ester was successful, although the product mixtures were generally more complex [26]. 

Zamifenacin may be also synthesized from L-proline methyl ester in 4 steps an overall yield of 20% by using a ring enlargement of L-proline derivative. 

The order of transformations was reversed to obtain the corresponding methyl ester 45. rrans-4-Hydroxy-L-proline methyl ester was prepared... 

Although this method proved successful for 4-keto-L-proline methyl ester 48, it was decided to investigate the conventional azeotropic dehydration method. Derivative 48 and pyrrolidine (1.2 equiv) were heated under reflux in benzene, collecting the water produced using a Dean and Stark apparatus. A quantitative yield of the corresponding enamine 52 was obtained after only 30 min (Scheme 19). Again, full assignment of NMR spectra was complicated by the apparent presence of rotameric structures. 

C6H11N02 L-proline methyl ester hydrochloride 2133-40-6 22.00 1.0359 2 8411 C6H120 3-methyl-2-pentanone 565-61-7 -106.00 1.0717 2... 

Poly(acryloyl-L-proline-methyl ester) Gentamicin, isoniazid, insulin [41]... 

Scheme 5 (a) A -Ethoxycarbonyl-fran5-4-hydroxy-L-proline methyl ester, PPTS, CH2CI2 (b) PhMgBr, THF (c) KOH (d)... 

FJFluoroproUne in Positron Emission Tomography There have been several reports of the synthesis of [ F]4-fluoro-L-proline. The first synthesis reported in 1983 involved reaction of tetraethylammonium [ FJfluoride with 4-A -tosly-4-trifluoromethanesulfonyloxy-L-proline methyl ester " (Fig. 3.17). Hamacher and coworkers reported the syntheses of no-carrier-added (NCA) cis-and tra 5 -[ F]4-fluoro-L-prolines by Kryptohx 222-mediated nucleophilic [ F] fluorination of cis- and trans- A-t-Boc-4-tosyloxy-L-prolines followed by... 

Figure 7. Lowered-symmetry sector rule projection of N-nitroso-L-proline methyl ester. The signs refer to the upper sectors. (Modified from Polonski and Prajer, 1976.)...

Poly(7V-acryloyl-L-proline methyl ester-6-7V-acryloyl-4-tra 5-hydroxy-L-proline) water 2010MO1... 

Poly(A -aciyloyl-L-proline methyl ester-6-A -acryloyl-4-ira 5 -hydroxy-L-proline)... 

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