1,5-Dimethyl 2-pentenedioate → HCID 53671068, compound

HRID 2398433Notes

Reaction equation

HRID 2398433 reaction equation
[N+:1]([C:4]1[CH:9]=[CH:8][C:7]([O:10][CH3:11])=[CH:6][C:5]=1[SH:12])([O-:3])=[O:2].[CH3:13][O:14][C:15](=[O:23])[CH:16]=[CH:17][CH2:18][C:19]([O:21][CH3:22])=[O:20]>>[CH3:22][O:21][C:19](=[O:20])[CH2:18][CH:17]([S:12][C:5]1[CH:6]=[C:7]([O:10][CH3:11])[CH:8]=[CH:9][C:4]=1[N+:1]([O-:3])=[O:2])[CH2:16][C:15]([O:14][CH3:13])=[O:23]

Participants

3

Reactant 2

HCID 2324901,5-Dimethyl 2-pentenedioateHCID 21435251HCID 21435251, compound

Product 1

HCID 53671068HCID 53671068, compound

Procedure

The starting material can be obtained by reaction of 2-nitro-5-methoxyphenol with N,N-dimethyl-thiocarbamoyl chloride in DMF in the presence of NaH to give 1-dimethylamino-thiocarbonyloxy-2-nitro-5-methoxyphenol (m.p. 125°), rearrangement, by heating for half an hour at 210°, to give 1-dimethylaminocarbonylmercapto-2-nitro-5-methoxyphenol (m.p. 101°), saponification with aqueous-ethanolic sodium hydroxide solution at 20° to give 2-nitro-5-methoxy-thiophenol (m.p. 87°), addition reaction with glutaconic acid dimethyl ester to give 3-(2-nitro-5-methoxy-phenylmercapto)-glutaric acid dimethyl ester (m.p. 91°), saponification to give the free acid (m.p. 165°-166°), cyclization to give 5-methoxy-8-nitro-thiochroman-4-one-2-acetic acid (m.p. 182°-183°), conversion into the amide (m.p. 228°-230°), and the nitrile (m.p. 164°-165°), ether cleavage to yield 5-hydroxy-8-nitro-thiochroman-4-on-2-acetonitrile (m.p. 187°-188°), hydrogenation on 5% Pd-C in methanol at 20° and normal pressure to give 5-hydroxy-8-amino-thiochroman- 4-one-2-acetonitrile (hydrochloride, m.p. 240° with decomposition), acetylation with ketene in dichloromethane/methanol to give 5-hydroxy-8-acetamidothiochroman-4-one-2-acetonitrile (m.p. 142°), reaction to give the aldehyde (m.p. 142°-144°) and condensation with 2-phenyl-2-thiazolin-5-one to give 2-phenyl-4-[2-(5-hydroxy-8-acetamidothiochroman-4-on-2-yl)-ethylidene]-2-thiazolin-5-one (m.p. 222°-224°), condensation with acetonedicarboxylic acid monomethyl ester-monoamide to give a mixture of stereoisomeric 4-thiobenzamido-1,4,4a,5,5a,6,11,12a-octahydro-3,10,12-trihydroxy-7-acetamido-1,11-dioxo-6-thianaphthacene-2-carboxamides (m.p. 238°-240° with decomposition), epimerization with pyridine at 40° to give a mixture (m.p. 228°-230° with decomposition) of 4-de-dimethylamino-4-thiobenzamido-7-acetamido-12a-de- hydroxy-6-thiatetracycline and its 5a-epimer, hydroxylation of the mixture and separation of the isomers via the imino ethers.

Workup

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Sources & evidence

ORD record
ord-bee43aa708784cdfac19aaa8e239966e
Source dataset
uspto-grants-1977_05
Patent number
US04024272

Reaction notes

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