Chemistry: molecular biology and microbiology – Micro-organism – tissue cell culture or enzyme using process... – Preparing heterocyclic carbon compound having only o – n – s,...
Patent
1986-03-31
1987-12-29
Daus, Donald G.
Chemistry: molecular biology and microbiology
Micro-organism, tissue cell culture or enzyme using process...
Preparing heterocyclic carbon compound having only o, n, s,...
435213, 435280, 548216, 549404, 549409, C12P 1706, C07P 4100, C07D31104
Patent
active
047161132
ABSTRACT:
An improved process for preparing (4S)-6-fluoro-spiro-[chroman-4,4'-imidazolidine]-2',5'-dione (sorbinil) or its (2R)-methyl derivative (2-methylsorbinil) is disclosed herein, starting from p-fluorophenol in each instance. The final products obtained have known pharmaceutical value as agents for the control of certain chronic diabetic complications. Key steps concerned with the process involve converting p-fluorophenol into the appropriate .beta.-(4-fluorophenoxy)alkane halide, followed by amidoalkylation with N-benzoyl or N-(lower alkanoyl)-.alpha.-hydroxyglycine to form an intermediate 2-amidoalkylated derivative thereof, and then dehydration and spiroalkylation of said intermediate by treatment with a dehydrating agent and a base to yield a spiroalkylated azlactone compound. The latter compound is then subsequently converted to the known 4-amino-6-fluorochroman-4-carboxylic acid or the novel (2R)-methyl derivative thereof, both in the form of their hydrohalide acid addition salts, by employing acid hydrolysis and the intermediate spiro-amino acid hydrohalide salt is thereafter converted to the corresponding methyl or ethyl ester and resolved with .alpha.-chymotrypsin to afford the desired (S)-methyl or (S)-ethyl ester. Treatment of either of these latter two esters with an alkali metal cyanate in an acid medium then effects conversion of same to the desired spiro-hydantoin ring compound. Alternatively, the spiro-amino acid hydrohalide salt can also be converted to the desired spiro-hydantoin ring compound in a known manner, involving a sequence of three reaction steps. The spiroalkylated azlactone compound of the instant invention, as well as the methyl and ethyl esters mentioned above, are themselves novel compounds and are valuable as synthetic intermediates in the process of this invention.
REFERENCES:
patent: 3878043 (1975-04-01), Matta et al.
patent: 4117230 (1978-09-01), Sarges
patent: 4130714 (1978-12-01), Sarges
patent: 4260684 (1981-04-01), Schutt
patent: 4262092 (1981-04-01), Bauer
patent: 4267342 (1981-05-01), Schnur
patent: 4339589 (1982-07-01), Steglich et al.
patent: 4389489 (1983-06-01), Preiss et al.
patent: 4435578 (1984-03-01), Cue, Jr. et al.
patent: 4439524 (1984-03-01), Schutt
patent: 4464380 (1984-08-01), Hutchinson
patent: 4474967 (1984-10-01), Sarges
Sakimae et al,, CA 103-36173t.
G. C. Finger et al., "Aromatic Fluorine Compounds, VIII. Plant Growth Regulators and Intermediates", Journal of the American Chemical Society, vol. 1, p. 94, (1954).
L. F. Fieser and M. Fieser, "Reagents for Organic Synthesis," vol. 1, John Wiley and Sons, Inc., New York, N.Y., 1967, p. 1160.
J. Bryan Jones and J. F. Beck, "Techniques of Chemistry", vol. X, (Applications of Biochemical Systems in Organic Chemistry), Jones, Sik and Perlman, Editors, John Wiley & Sons, Inc., New York, N.Y., 1970, Chapter 4.
D. Ben-Ishai, et al., "A New Synthesis of N-Acyl Aromatic .alpha.-Amino Acids; Amidoalkylation of Aromatic Compounds with Glyoxylic Acid Derivatives", Journal of the Chemical Society, Chemical Communications, p. 349, (1975).
D. Ben-Ishai et al., "The Synthesis of p-Substituted D,L-Phenylglycines by the Amidoalkylation of Benzyl Chloride and N-Benzylamide", Tetrahedron, vol. 33, p. 2715, (1977).
Akers Lawrence C.
Daus Donald G.
Pfizer Inc.
Richardson Peter C.
Shen Cecilia
LandOfFree
Process for the production of an (S)-methyl or (S)-ethyl 4-amino does not yet have a rating. At this time, there are no reviews or comments for this patent.
If you have personal experience with Process for the production of an (S)-methyl or (S)-ethyl 4-amino, we encourage you to share that experience with our LandOfFree.com community. Your opinion is very important and Process for the production of an (S)-methyl or (S)-ethyl 4-amino will most certainly appreciate the feedback.
Profile ID: LFUS-PAI-O-462924