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【结 构 式】

【分子编号】37004

【品名】6-hydroxy-2,2,5,5-tetramethylcyclohexanone

【CA登记号】

【 分 子 式 】C10H18O2

【 分 子 量 】170.25172

【元素组成】C 70.55% H 10.66% O 18.79%

与该中间体有关的原料药合成路线共 1 条

合成路线1

该中间体在本合成路线中的序号:(III)

Fischer esterification of 2,2,5,5-tetramethylhexanedioic acid (I) provided diethyl ester (II), which was subjected to acyloin condensation with sodium in xylene to furnish the alpha-hydroxy cyclohexanone (III). Further oxidation of (III) with CrO3 gave diketone (IV). This was condensed with 2,3-diaminopropionic acid (V) to afford, after esterification with MeOH and H2SO4, the quinoxaline ester (VI). Reduction of (VI) to alcohol (VII) employing diisobutylaluminum hydride, followed by Swern oxidation gave rise to aldehyde (VIII). Optionally, addition of vinylmagnesium bromide to (VIII), and further Swern oxidation of the allylic alcohol (IX) provided the alpha,beta-unsaturated ketone (X). Conversion to the required diketo precursor (XII) was achieved by two related strategies. Coupling of ethyl 4-formylbenzoate (XI) with the unsaturated ketone (X) using 3-benzyl-5-(2-hydroxyethyl)-4-ethylthiazolium chloride as the catalyst gave the 1,4-diketone (XII). Alternatively, addition of vinylmagnesium bromide to ethyl 4-formylbenzoate (XI) followed by oxidation with pyridinium dichromate gave unsaturated ketone (XIII). This was then coupled with quinoxaline aldehyde (VIII) in the presence of a thiazolium salt to furnish diketone (XII).

1 Tai, K.; Yamauchi, T.; Hida, T.; Kikuchi, K.; Nagia, M.; Yoshimura, H.; Tokuhara, N.; Hibi, S.; Synthesis and structure-activity relationships of 5,6,7,8-tetrahydro-5,5,8,8-tetramethyl-2-quinoxaline derivatives with retinoic acid receptor alpha agonistic activity. J Med Chem 2000, 43, 3, 409.
2 Kikuchi, K.; Tagami, K.; Yoshimura, H.; Hibi, S.; Nagai, M.; Abe, S.; Okita, M.; Hida, T.; Higashi, S.; Tokuhara, N.; Kobayashi, S. (Eisai Co., Ltd.); Heterocyclic carboxylic acid derivs. and drugs containing the same. JP 1997071566; US 5977108; WO 9702244 .
中间体序号 中间体编号 品名 CAS号 分子式 供应商 用于合成
16524 bromo(vinyl)magnesium 1826-67-1 C2H3BrMg 详情 详情
(I) 37002 2,2,5,5-tetramethylhexanedioic acid C10H18O4 详情 详情
(II) 37003 diethyl 2,2,5,5-tetramethylhexanedioate C14H26O4 详情 详情
(III) 37004 6-hydroxy-2,2,5,5-tetramethylcyclohexanone C10H18O2 详情 详情
(IV) 37005 3,3,6,6-tetramethyl-1,2-cyclohexanedione C10H16O2 详情 详情
(V) 37006 2,3-diaminopropionic acid 18635-45-5 C3H8N2O2 详情 详情
(VI) 37007 methyl 5,5,8,8-tetramethyl-5,6,7,8-tetrahydro-2-quinoxalinecarboxylate C14H20N2O2 详情 详情
(VII) 37008 (5,5,8,8-tetramethyl-5,6,7,8-tetrahydro-2-quinoxalinyl)methanol C13H20N2O 详情 详情
(VIII) 37009 5,5,8,8-tetramethyl-5,6,7,8-tetrahydro-2-quinoxalinecarbaldehyde C13H18N2O 详情 详情
(IX) 37010 1-(5,5,8,8-tetramethyl-5,6,7,8-tetrahydro-2-quinoxalinyl)-2-propen-1-ol C15H22N2O 详情 详情
(X) 37011 1-(5,5,8,8-tetramethyl-5,6,7,8-tetrahydro-2-quinoxalinyl)-2-propen-1-one C15H20N2O 详情 详情
(XI) 10170 methyl 4-formylbenzoate 1571-08-0 C9H8O3 详情 详情
(XII) 37012 methyl 4-[4-oxo-4-(5,5,8,8-tetramethyl-5,6,7,8-tetrahydro-2-quinoxalinyl)butanoyl]benzoate C24H28N2O4 详情 详情
(XIII) 35857 methyl 4-acryloylbenzoate C11H10O3 详情 详情
Extended Information