Benzyloxycarbonyl-L-proline

The benzyloxycarbonyl-L-proline thus obtained (180 g) is dissolved in a mixture of dichloro-methane (300 ml), liquid isobutylene (800 ml) and concentrated sulfuric acid (7.2 ml). The solution is shaken in a pressure bottle for 72 hours. The pressure is released, the Isobutylene is allowed to evaporate and the solution is washed with 5% sodium carbonate, water, dried over magnesium sulfate and concentrated to dryness in vacuo, to obtain benzyloxycarbonyl-L-proline tert-butyl ester, yield 205 g. 

Benzyloxycarbonyl-L-proline tert-butyl ester (205 g) is dissolved in absolute ethanol (1.2 ) and hydrogenated at normal pressure with 10% Pd on carbon (10 g) until only a trace of carbon dioxide is observed in the hydrogen exit gas (24 hours). The catalyst is filtered off and the filtrate is concentrated in vacuo at 30 mm Hg. The residue is distilled in vacuo, to obtain L-proline tert-butyl ester, BPimm... 

C 3H,5N04 1148-11-4) see Angiotensinamide Captopril 7V-benzyloxycarbonyl-L-proline tert-butyl ester (C17H23NO4 16881-39-3) see Captopril 7V-benzyloxycarbonyl-L-serine (CiiHijNOj 7745-80-8) see Nelfinavir mesylate iV-benzyloxycarbonyl-L-serine-P-lactone (C Hi,N04 26054-60-4) see Nelfinavir mesylate 7V-benzyloxycarbonylsuccinimide... 

The reaction of iV-benzyloxycarbonyl L-proline acid chlorides 134 with imine 135 in the presence of triethylamine, at room temperature, gave the corresponding spiro-(3-lactams 136, 137 as a 1 1 mixture of diastereoisomers, which were separated by column chromatography. The Staudinger reaction proceeds with complete stereoselectivity with a cis relative disposition of the pyrrolidine nitrogen and the phenyl group, but no asymmetric induction was observed. However, very... 

Benzyloxycarbonyl-L-proline. Dissolve 4.6 g (0.04 mol) of L-proline (Expt 5.186) in 10 ml (0.04 mol) of 4 m sodium hydroxide solution, cool to 0 °C in an ice bath, and add 7.0 g (0.041 mol) of benzyl chloroformate and 10 ml (0.04 mol) of 4 m sodium hydroxide solution alternately and portionwise, with shaking and cooling, during 30 minutes. Allow the mixture to warm to room temperature with intermittent shaking during 1 hour, extract with 2 x 15-ml portions of ether, and acidify the aqueous phase (Congo red) with dilute (1 1) hydrochloric acid. Extract the liberated oil with 4 x 10-ml portions of ether, dry over anhydrous sodium sulphate, and remove the ether to obtain 8.8 g (88%) of benzyloxycarbonyl-L-proline which crystallises slowly. A sample recrystallised from ether-light petroleum (b.p. 40-60 °C) has m.p. 75 °C. 

In contrast, reduction of a-(A-diphenylphosphinylamino)vinylphosphonate in the presence of the same catalyst proceeded very slowly and gave the saturated product with a low enantiomeric excess (e.e. 3% of the 5 -isomer) (equation 106). Reduction of the same enamidophosphonate with NaBH4 in the presence of A-benzyloxycarbonyl-L-proline gave the opposite aminophosphonate enantiomer in a higher excess. 

This protocol was also applied to diazepam derivatives 6 [49]. When these compounds were treated with N-benzyloxycarbonyl-L-proline acid chloride and tetrahydrofuroyl chloride, the expected spirocyclic systems 7 (Scheme 2) were obtained in good yields. In the case of the N-benzyloxycarbonyl-L-proline acid chloride, the reaction was carried out at room temperature, while the process involving the tetrahydrofuroyl chloride needed to be performed in refluxing toluene. This higher temperature was the likely cause of the loss of selectivity observed in the latter case, in which a 10 1 mixture of diastereoisomers was obtained. 

Triethylamine and sec-butyl chloroformate added dropwise at -15° to a stirred ethereal soln. of N-benzyloxycarbonyl-L-proline, the resulting triethylamine hydrochloride removed by filtration, ethereal diazomethane added dropwise, stirred 4 hrs. at 0°, and allowed to stand overnight in a refrigerator a-diazoketone (Y 91%) dissolved in methanol, and refluxed 12 hrs. with AggO on a water bath -> methyl N-benzyloxycarbonyl- -L-homoprolinate (Y 95.1%). L. Balaspiri et al., Helv. 58, 969 (1975) / -lysine deriv. cf. T. Wakamiya et al.. Bull. Chem. Soc. Japan 48, 2401 (1975). 

The one-step modified Curtius reaction of IV-benzyloxycarbonyl-L-proline (80) gives the allophanate (82) as the major product in addition to the expected urethane (81a). However, die use of r-butyl carbamate (83) as an additive changes the reaction course and the desired carbamate (81b), though accompanied by racemization, is obtained in good yield. Similarly, the -carboline derivative (84) also affords a mixture of the urethane (85) and the allophanate (86), with the latter as the major product, by a one-step procedure. The two-step procedure, however, produces more of the urethane (85 Scheme 20). 

Isobutyl chloroformate added at —5° to a soln. of benzyloxycarbonyl-L-proline and triethylamine in dry chloroform, stirred 0.5 hr., L-leucine p-nitrophenyl ester hydrobromide added followed by gradual addition of a soln. of triethylamine in chloroform over a period of 15 min., kept 3 hrs. at 0-10° and 1 hr. at room temp., then glycine ethyl ester hydrochloride and triethylamine added with stirring, and kept 2 days at room temp. -> benzyloxycarbonyl-L-prolyl-L-leucylglycine ethyl ester. Y 84%.—The difunctionality of aminoacid active esters and the different reaction rates at the amino and ester ends allow the direct synthesis of tripeptides by two consecutive reactions. F. e., also isolation of intermediates, s. M. Goodman and K. G. Stueben, Am. Soc. 81, 3980 (1959). Peptide synthesis... 

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