2-oxetanone -Drug Synthesis Database

【结构式】

【分子编号】24477

【品名】2-oxetanone

【CA登记号】57-57-8

【分子式】C₃H₄O₂

【分子量】72.06356

【元素组成】C 50% H 5.59% O 44.4%

与该中间体有关的原料药合成路线共 2 条

合成路线1 合成路线2

合成路线1

该中间体在本合成路线中的序号：(VI)

The reaction of 7-bromo-3a,8b-cis-3a,8b dihydro-3H-5-cyclopenta[b]benzofurancarboxylic acid (I) with trioxane and H2SO4, followed by methylation with diazomethane and debromination with H2 over Pd/C, gives the hydroxymethyl compound (II), which is protected with 1,1-diethoxyethane and p-toluenesulfonic acid to give the protected ester (III). Reduction of the ester (III) with LiAlH4 in THF affords the corresponding hydroxymethyl compound (IV), which by reaction with SOCl2 in DMF is converted to the chlorometnyl derivative (VI). The condensation of (V) with beta-propiolactone (VI) by means of Mg in TFH gives the phenylbutyric acid (VII), which by methylation with diazomethane and deprotection with HCl in metnanol yields the dihydroxyester (VIII). Selective acetylation of (VIII) by reaction with trimethyl-tert-butylchlorosilane, then with acetic anhydride and final desilylation with acetic acid affords methyl 4-(2alpha-acetoxy-1-hydroxymethyl-2,3,3a,8b-tetrahydro-1H-cyclopenta[b]benzofuranyl)butyrate (IX), which is oxidized with DMSO. dicyclohexylcarbodiimide (DCC) and trifluoroacetic acid to the corresponding aldehyde (X). The Wittig condensation of (X) with dimethyl 3-methyl-2-oxohept-5-yn-1-yl phosphonate (XI) by means of NaH in DMF affords 11,15-dideoxy-11-acetoxy-16-methyl-15-oxo-18,19-tetradehydro-5,6,7-trinor-4,8-inter-m-phenylene-prostaglandin I2 methyl ester (XII), vvhich is reduced with cerium chloride and NaBH4 in methanol to the corresponding 15-hydroxy compound (XIII). Finally, this compound is deacetylated and saponified as usual.

参考文献中间体

合成目标

【1】 Matsumoto, K.; Nagase, H.; Ohno, K. (Toray Industries, Inc.); Preparation of 5,6,7-trinor-4,8-inter-m-phenylene pgi2derivative. JP 1984134787 .
【2】 Ohno, K.; Nagase, H.; Matsumoto, K.; Nishio, S. (Toray Industries, Inc.); 5,6,7-Trinor-4,8-inter-m-phenylene protaglandin I2 derivatives useful in anti-ulcer, hypotensive and platelet aggregation inhibiting compositions. EP 0084856; JP 58124778; US 4474802 .
【3】 Castaner, J.; Prous, J.; TRK-100. Drugs Fut 1986, 11, 11, 956.

中间体序号	中间体编号	品名	CAS号	分子式	供应商	用于合成
(I)	24472	(3aS,8bS)-7-bromo-3a,8b-dihydro-3H-cyclopenta[b][1]benzofuran-5-carboxylic acid		C₁₂H₉BrO₃	详情	详情
(II)	24473	methyl (3aS,8bS)-2-hydroxy-1-(hydroxymethyl)-3a,8b-dihydro-3H-cyclopenta[b][1]benzofuran-5-carboxylate		C₁₄H₁₄O₅	详情	详情
(III)	24474	methyl (4aR,5aS,10bS,10cS)-3-methyl-1,4a,5,5a,10b,10c-hexahydro[1,3]dioxino[5',4':3,4]cyclopenta[1,2-b][1]benzofuran-7-carboxylate		C₁₆H₁₈O₅	详情	详情
(IV)	24475	[(4aR,5aS,10bS,10cS)-3-methyl-1,4a,5,5a,10b,10c-hexahydro[1,3]dioxino[5',4':3,4]cyclopenta[1,2-b][1]benzofuran-7-yl]methanol		C₁₅H₁₈O₄	详情	详情
(V)	24476	(4aR,5aS,10bS,10cS)-7-(chloromethyl)-3-methyl-1,4a,5,5a,10b,10c-hexahydro[1,3]dioxino[5',4':3,4]cyclopenta[1,2-b][1]benzofuran		C₁₅H₁₇ClO₃	详情	详情
(VI)	24477	2-oxetanone	57-57-8	C₃H₄O₂	详情	详情
(VII)	24478	4-[(4aR,5aS,10bS,10cS)-3-methyl-1,4a,5,5a,10b,10c-hexahydro[1,3]dioxino[5',4':3,4]cyclopenta[1,2-b][1]benzofuran-7-yl]butyric acid		C₁₈H₂₂O₅	详情	详情
(VIII)	24479	methyl 4-[(2R,3aS,8bS)-2-hydroxy-1-(hydroxymethyl)-2,3,3a,8b-tetrahydro-1H-cyclopenta[b][1]benzofuran-5-yl]butanoate		C₁₇H₂₂O₅	详情	详情
(IX)	63079	methyl 4-[(2R,3aS,8bS)-2-(acetyloxy)-1-(hydroxymethyl)-2,3,3a,8b-tetrahydro-1H-cyclopenta[b][1]benzofuran-5-yl]butanoate		C₁₉H₂₄O₆	详情	详情
(X)	24481	methyl 4-[(2R,3aS,8bS)-2-(acetoxy)-1-formyl-2,3,3a,8b-tetrahydro-1H-cyclopenta[b][1]benzofuran-5-yl]butanoate		C₁₉H₂₂O₆	详情	详情
(XI)	24482	dimethyl 3-methyl-2-oxo-5-heptynylphosphonate		C₁₀H₁₇O₄P	详情	详情
(XII)	24483	(2R,3aS,8bS)-4-[2-Acetoxy-1-(4-methyl-3-oxooct-1(E)-en-6-ynyl)-2,3,3a,8b-tetrahydro-1H-cyclopenta[b]benzofuran-5-yl]butyric acid methyl ester; (2R,3aS,8bS)-4-[2-Acetoxy-1-(4-methyl-3-oxooct-1(E)-en-6-ynyl)-2,3,3a,8b-tetrahydro-1H-cyclopenta[b]benzofuran-5-yl]butyric acid methyl ester		C₂₆H₃₂O₄	详情	详情
(XIII)	24484	methyl 4-[(2R,3aS,8bS)-2-(acetoxy)-1-[(E,3S)-3-hydroxy-4-methyl-1-octen-6-ynyl]-2,3,3a,8b-tetrahydro-1H-cyclopenta[b][1]benzofuran-5-yl]butanoate		C₂₇H₃₄O₆	详情	详情

合成路线2

该中间体在本合成路线中的序号：(II)

Condensation of 4-ethylaniline (I) with propiolactone (II) produces the beta-aminoacid (III). Intramolecular Friedel-Crafts cyclization of (III) by means of polyphosphoric acid leads to the quinolinone (IV). Then, electrophilic iodination of (IV) by using iodine monochloride provides the intermediate (V)

参考文献中间体

合成目标

【1】 Jarvest, R.L.; Berge, J.M.; Berry, V.; et al.; Nanomolar inhibitors of Staphylococcus aureus methionyl tRNA synthetase with potent antibacterial activity against Gram-positive pathogens. J Med Chem 2002, 45, 10, 1959.
【2】 Berge, J.M.; Forrest, A.K.; Elder, J.S.; Jarvest, R.L. (GlaxoSmithKline plc); Quinolones as t-RNA synthetase inhibitors and antibacterial agents. WO 0021949 .

中间体序号	中间体编号	品名	CAS号	分子式	供应商	用于合成
(I)	60623	4-ethylaniline; 4-ethylphenylamine		C₈H₁₁N	详情	详情
(II)	24477	2-oxetanone	57-57-8	C₃H₄O₂	详情	详情
(III)	60624	3-(4-ethylanilino)propanoic acid		C₁₁H₁₅NO₂	详情	详情
(IV)	60625	6-ethyl-2,3-dihydro-4(1H)-quinolinone		C₁₁H₁₃NO	详情	详情
(V)	60626	6-ethyl-8-iodo-2,3-dihydro-4(1H)-quinolinone		C₁₁H₁₂INO	详情	详情

Extended Information