3-Oxo-3- propionic acid

Beccalli et al. reported a new synthesis of staurosporinone (293) from 3-cyano-3-(lH-indol-3-yl)-2-oxo propionic acid ethyl ester (1464) (790). The reaction of 1464 with ethyl chlorocarbonate and triethylamine afforded the compound 1465, which, on treatment with dimethylamine, led to the corresponding hydroxy derivative 1466. The triflate 1467 was prepared from 1466 by reaction with trifluoromethanesulfonic anhydride (Tf20) in the presence of ethyldiisopropylamine. The palladium(O)-catalyzed cross-coupling of the triflate 1467 with the 3-(tributylstannyl)indole 1468 afforded the vinylindole 1469 in 89% yield. Deprotection of both nitrogen atoms with sodium ethoxide in ethanol to 1470, followed by photocyclization in the presence of iodine as the oxidizing agent provided the indolocarbazole 1471. Finally, reductive cyclization of 1471 with sodium borohydride-cobaltous chloride led to staurosporinone (293) in 40% yield (790) (Scheme 5.248). 

Aromatization of 8-(cyano or ethoxycarbonyl)-2-oxo-2,3,4,4a,7,8-hexa-hydropyrido[l,2-A][l,2]oxazine-8-carbonitriles 12 by treatment with CS2CO3 resulted the formation of (2-pyridyl)propionic acids 13 (00OL4007). Application of other bases, e.g. DBU, NEt3, Dowex 1X8-400 ion-exchange resin afforded (2-pyridyl)propionic acids in irreproducible or considerably lower yields. 

The reaction of potassium 3-amino-4-oxo-3,4-dihydroquinazoline-2-thiolate 62 with a-bromophenylacetic acid 63 resulted in the formation of (3-amino-4-oxo-3,4-dihydroquinazolin-2-ylsulfanyl)-phenyl-acetic acid methyl ester 64 which on alkali treatment and subsequent acidification resulted in the synthesis of 2-phenyl- 1-thia-4,4a,9-triaza-anthracene-3,10-dione 65 <1999JCR(S)86>. Similarly, the reaction of potassium 3-amino-5,6-dimethyl-4-oxo-3,4,4a,7a-tetrahydrothieno[2,3- pyrimidine-2-thiolate 66 with a-bromo-ester 67 resulted in the formation of 2-(3-amino-5,6-dimethyl-4-oxo-3,4,4a,7a-tetrahydrothieno[2,3- / pyrimidin-2-ylsulfanyl)-propionic acid ethyl ester 68. Subsequent treatment with alkali followed by acidification resulted in the formation of 2,3,7-trimethyl-3a,9a-dihydro-l,8-dithia-4a,5,9-triazacyclopenta[ ]naphthalene-4,6-dione 69 <2000JHC1161>... 

A number of syntheses of pyrrolizidine derivatives are based on cyclization of amino acids such as /3-(pyrrolidin-2-yl)propionic acid, 4-aminopimelic acid, and their homologues to give 3-oxo- and 3,5-dioxo-pyrrolizidines. Reduction of these cyclic amides leads to pyrrolizidines. 

Claisen condensation of ethyl quinuclidine-2-carboxylate (73) with ethyl acetate yields ethyl j8-oxo-j8-(2-quinuclidyl)propionate (84). This was transformed into j8-amino-j3-(2-quinuclidyl)propionic acid (85)108 and 2-acetylquinuclidine (86).43... 

Cyclosporin (Section 16.1.3) is an undecapeptide that acts as a potent immunosuppressant. Seven of its eleven residues are N-methylated. Its synthesis in solution was carried out by a series of segment condensations)32,33 The didemnins (Section 16.1.4) are isolated from marine organisms known as tunicates. Their therapeutic potential lies in applications as antitumor, antiviral, and immunosuppressant agents. The didemnin family of natural products contains peptidomimetic residues including A,0-dimethyltyrosine-proline and leucine—2-(hydroxyisovaleryl)propionic acid and (4-hydroxy)-2,5-dimethyl-3-oxo-... 

Figure 3.5. 36-Cascade tricyclo[3.3.1.13,7]decane[4-l,3,5,7 (3-oxo-2-azapropylidyne) (3-oxo-2-azapentylidyne) propionic acid.

Zinc foam (100 g) was shaken for 5 min with mercury(n) chloride (10 g), concentrated hydrochloric acid (5 ml), and water (150 ml), then the aqueous layer was poured off, and the amalgamated zinc was treated with water (75 ml), concentrated hydrochloric acid (175 ml), toluene (100 ml), and the carbonyl compound to be reduced (50 g). When necessary, glacial acetic acid (3-5 ml) may be added to increase the solubility in the aqueous layer. The mixture is heated to brisk ebullition under reflux. At each of three 6-hourly intervals hydrochloric acid (50 ml) is added, the total time of boiling being thus about 24 h. As examples, 3-oxo-3-phenyl-, -3-m-tolyl-, -3-p-tolyl-, -3-(l-naphthoyl)-, and -3-(2-naphthoyl)-propionic acid, benzoylnaphthalene, 2-acetylnaphthalene among other materials were reduced more satisfactorily than in absence of toluene. A comparison of the toluene method with the old method is provided, for instance, by Martin who obtained a 72-78 % yield in a preparation by himself by the old method, compared with 90% by the new method. 

With the exception of acetic, acryUc, and benzoic all other acids in Table 1 are primarily produced using oxo chemistry (see Oxo process). Propionic acid is made by the Hquid-phase oxidation of propionaldehyde, which in turn is made by appHcation of the oxo synthesis to ethylene. Propionic acid can also be made by oxidation of propane or by hydrocarboxylation of ethylene with CO and presence of a rhodium (2) or iridium (3) catalyst. 

Propionic acid, 2-iodo-3-nitro-, ethyl ester [Propanoic acid, 2-iodo-3-mtro-, ethyl ester], 65 2//-Pyran, 3,4-dihydro-, 51 2//-PYR AN-2-ONE, 49 2H Pyran 2-one, 5 bromo 5,6-dihydro, 50 27/-PYRAN-2-ONE, 5,6 DIHYDRO-, 49 PYRIDINE, 2,3,4,5 TETRAHYDRO, 118 Pyridines, -substituted, 34 a Pyrone-6-carboxyhc acid [2H Pyran-6-Larboxyhc acid 2-oxo ], 51 Pyrroles, 34... 

Reactions of 2,3-dioxo-l,2,3,5,6,7-hexahydropyrido[l,2,3-carboxylic acids and the homologous acetic and propionic acids, prepared by basic hydrolysis of the corresponding ester, with amines, 28% NH4OH, and hydroxylamine derivatives in the presence of l-ethyl-3-[3-(dimethylamino)propyl]carbodiimide and hydroxybenztria-zole <1995BML1527>, 1995BML1533>, and in the presence of NEt3 and A, A -bis(2-oxo-3-oxazolidinyl)phosphinic... 

XX Zhang, F Hong, WB Chang, YX Ci, YH Ye. Enantiomeric separation of promethazine and D,L-a-amino-/3-[4-(l,2-dihydro-2-oxo-quinoline)] propionic acid drugs by capillary zone electrophoresis using albumins as chiral selectors. Anal Chim Acta 392 175-181, 1999. 

In the second method (Scheme 26) a 3-oxo ester is synthesized from an acid chloride and 2,2-dimethyl-l,3-dioxane-4,6-dione. Then, reductive amination of the 3-oxo ester with a-methyl(phenyl)methylamine provides a 3-amino- 3-alkyl propionic acid ester. This compound is then converted into the corresponding aldehyde, which is condensed with an eno-late to afford the final product. A representative synthetic procedure of this method is given in detail. 

Baltrusis and Beresnevicius205 found that a mixture of 2-amino-5-chloropyridine and methyl acrylate in acetic acid in a sealed tube at 100 C gives 4-oxo-2,3-dihydro-4H-pyrido[l,2-a]pyrimidine (147 X = Cl) and the propionic acid (144 R = 5-0, R1 = H), but at room temperature the mixture instead gives 2-oxo-3,4-dihydro-2//-pyrido[l,2-a]pyrimidine (142 R = 7-C1) and the propionate (144 R = 5-0, R1 = Me). Compound (147 X = Cl)... 

OHDPAT, 8-hydroxy-2(di- -propylamino)tetralin ACPD, trans-1 -amino-cyclopenty 1 -1,3 -dicarboxylate AMP A, DL-cr-amino-3-hydroxy-5-methylisoxazole-4-propionate BIMU8, [endo-A-8-methyl-8-azabicyclo(3.2.1)oct-3-yl]-2,3-dihydro-3-isopropyl-2-oxo-177-benzimidazol-l-carboxamide hydrochloride CGP 35348, 3-aminopropyl(diethoxymethyl)phosphinic acid CNQX, 6-cyano-7-nitroquinoxaline-2,3-dione CP 99994, (+)-(2 , 3A)-3-(2-methoxybenzylamino)-2- ... 

A mixture of 5 parts l-(3-cyano-3,3-diphenylpropyl)-4-(2-oxo-l-benzimidazolinyl)piperidine, 7.5 parts propionic acid anhydride and 80 parts benzene is stirred and refluxed for 16 hours. After cooling, the reaction mixture is washed twice with 100 parts water. The aqueous layer is dried over potassium carbonate, filtered and evaporated. The residue is recrystallized from 60 parts of ether, yielding 4 parts crude l-(3-cyano-3,3-diphenylpropyl)-4-(2-oxo-3-propionyl-l-benzimidazolinyl)piperidine. This crop is recrystallized from 20 parts m-methyl-2-pentanone 4-ethyl-2-pentanone, yielding l-(3-... 

Oxo-cyclohexyl)phenyl]propionic acid Hydroxylamine hydrochloride... 

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