An efficient synthesis and mechanism of formation of 6-acetyl-1,2-dihydro-2-oxo-3-pyridinecarboxylic acid (original) (raw)
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International Journal of Advanced Research
Scheme-1 Prop-2-yn-1-yl 3-((tert-butoxycarbonyl)amino)-2,2-dimethylpropanoate Step-1 Dicyclohexylcarbodiimide (1.1 eq.) and triethylamine (2 eq.) were added to a stirred solution of compd-1 (1 eq.) and Compd-2 (1 eq.) in 1 : 1 ratio of Dichloromethane (DCM) : Dimethylformamide (10 mL/ 1 g) at 0°C. The reaction mixture was stirred at room temperature for 16 hours. After completion of reaction (checked by TLC), solid waste was filtered. The resultant filtrate was diluted with DCM, followed by washing with water, dried over anhydrous sodium sulphate (Na2SO4) and concentrated. The obtain crude material was purified by Silica gel (100-200 mesh) column chromatography using (2:8) ethyl acetate in hexane.
Journal of the American Chemical Society, 1961
glass funnel. I n this manner there was obtained 0.70 g. of salt (98.6y0, calculated as 1 equiv. of NaCl and 1 equiv. of disodium succinate). The salt was titrated at 35' (see pK.' determination). The titration curve obtained after correction for a water blank was identical (PH 2.3 to 7. 5) with that obtained on titration of an authentic sample of disodium succinate. In a similar manner a 75y0 yield of sodium acetate was obtained from Ia and identified titrimetrically (pK, 4.5). Reaction of Mono-4-imidazolylmethyl Succinate Hydrochloride (Ib) with Sodium Hydroxide.-In a 200-ml. roundbottomed flask was placed 1.0 g. (0.0043 mole) of mono-4imidazolylmethyl succinate hydrochloride. T o this was qdded 50 ml. of water. The solution was heated to 75' by means of a water-bath and 0.73 9;. (0.013 mole) of potassium hydroxide dissolved in 10 ml. of water mas added. The mixture was heated for 45 minutes. The solution was evaporated to dryness by flash evaporation and ethanol added to the residue. The mixture then was filtered. The filtrate was evaporated to dryness and the residue taken up in water. The solution was made acid with dilute hydrochloric acid, charcoaled, filtered, and evaporated l o dryness by flash evaporation. The residue mas dissolved in a small volume of ethanol and filtered. Addition of ether t o the filtrate resulted in a precipitate which appeared semi-crystalline but which became quite oily when the so!vent was removed. The material was chromatographed for 9.5 hr. on IVhatman #I paper using as solvent a 3 : 1 mixture of n-propyl alcohol and 1.0 N acetic acid.23 The chromatogram was developed, after air-drying, by the Pauli spray, as given by Ames and M i t~h e l l. 2~ A compound capable of coupling with diazotized sulfanilic acid and possessing the same Rf (0.77) as a standard of 4 (5)-h~d r o s~methylimidazole hydrochloride was identified as a major component.
Aldol Reactions of Pyroglutamates: Chiral Synthesis of 4a(S)- and 4�(R)-(Arylmethyl)pyroglutamates
Cheminform, 1992
Recipicstc Solution workup and 4 chromarography (+2: 54 mg (19%) (+)-2: 140 mg (49%) [ a ]~-134' (84% W) ID +5OO (31% ee) 1 4 crysrdlization (-1-2: 37 mg (13% overall) (+>2: 62 mg (22% overall) [ a ]~-1590 (-10046 et) [ a ]~ +158O (-10046 CC) 4 (144 mg) + 5 (143 mg) Recipifatc coupling A Solution workup and 4 chromatography (-)-3 122 mg (43%) (+)-3 121 mg (42%) [a],-540 (46% cc) [a], +540 (46% ee) Crystals: 26%; [ab-3O crystals: 21% [a], +40 Mother liq,: 74%; [ a ]~-72O (61% ee) Mother liq.: 78%; [a], +73O (62% ee) 4 4 crydlizarion of mother liquors (-)-3 66 mg (23% overall) (+)-3: 68 mg (24% overall) [ a l~-1170 (2 98% et) [ a ]~ +I 16' (-97% CC) at rt for 20 h under an argon atmosphere. Then concd HCl(5 mL) was added, followed by water (100 mL). The precipitate was filtered off, suspended in acetone with silica gel (20 g), and chromatographed on a silica gel column (40 g) using a light petmleum-ether mixture (1:l) as eluent. The eluate was evaporated to afford 1 (43 mg; 14%): mp 205-207 "C (no depression was observed for a mixture with an authentic sample of enantiome r i d y pure 1); [a]D-No (c 5.0, THF; 100% ee) 0it.U mp 207-209 "C and ["ID-35.5" or-33.4O, respectively, for optically pure compound and [ a ] D +34.3" for the enantiomer.) Analogous workup of the solution furnished 1 (121 mg; 42%): mp 210-214 (B) By Deracemization of (&)-l. To a degassed solution of CuC12.4H20 (200 mg; 1 mmol) in methanol (10 mL) was added a solution of (-)-sparteine (468; 2 mmol) in methanol (10 mL), and the mixture was stirred at rt for 10 min under argon. A solution of (&)-I (286 mg; 1 mmol) in degassed methanol (10 mL) was added, and the mixture was stirred under argon at rt for 20 h. The mixture was then worked up as above to give 1 (267 mg; 94%): mp 212-214 OC; [ a ] D-27.2' (c 5.0, THF; 80% ee). For further resolution, see the text. (R)-(+)and (S)-(-)-2,2'-Diamino-l,l'-binaphthyl (2). (A) By Coupling. A mixture of (-)-sparteine (702 mg; 3 "01) and 2-naphthylamine (286 mg; 2 mmol) in degassed methanol (15 mL) was added to a solution of CuC12.4H20 (400 mg; 2 mmol) in degassed methanol (15 mL), and the mixture was stirred under argon at rt for 4 h. The precipitate was filtered off, washed with methanol (5 mL), decomposed with concd HCl(3 mL), and then neutralized by concd aqueous ammonia (15 mL) and water (100 mL). The crude solid product (67 mg; 24%) was chromatographed as described for the first experiment to yield enriched (-)-2 (54 mg; 19%): mp 235-239 OC; ["ID-134' (c 2.0, pyridine; 84% ee). On single crystallization from acetic acid, this crop gave enantiomerically pure (-1-2 (27 mg; 13% overall). The mother liquor from the reaction was worked up separately in the same way and furnished enriched (+)-2 (140 mg; 49%): mp 184-216 OC; [ a ] D +50° (c 5.0, pyridine; 31% ee). Further resolution furnished enantiomerically pure (+)-2 (62 mg; 22% overall): mp 245-246 OC; [ a ]~-6.8' (C 5.0, THF; 20% ee).