|
【结 构 式】 
|
【分子编号】55202 【品名】tert-butyl (4R)-4-{[methoxy(methyl)amino]carbonyl}-2,2-dimethyl-1,3-oxazolidine-3-carboxylate 【CA登记号】 |
【 分 子 式 】C13H24N2O5 【 分 子 量 】288.34404 【元素组成】C 54.15% H 8.39% N 9.72% O 27.74% |
合成路线1
该中间体在本合成路线中的序号：(LIX)In a different procedure, addition of the allyl Grignard reagent (LX) to the N-methoxy amide (LIX), provided ketone (LXI). Subsequent addition of methylmagnesium chloride to (LXI) led to the tertiary alcohol (LXII), which was converted to the methyl ether (LXIII) by alkylation with iodomethane and NaH. Acetonide (LXIII) hydrolysis with p-toluenesulfonic acid in MeOH gave the N-Boc amino alcohol (LXIV). The olefin double bond of (LXIV) was then hydrogenated over Pd/C to the propyl derivative (LXV). Oxidation of alcohol (LXV) under modified Swern conditions furnished aldehyde (LXVI). This was then condensed with p-methoxybenzyl hydroxylamine (LXVII), leading to the nitrone (LXVIII).
| 【1】 Hanessian, S.; et al.; Total synthesis of A-315675: A potent inhibitor of influenza neuraminidase. J Am Chem Soc 2002, 124, 17, 4716. |
| 【2】 Inhibitors of neuraminidases. WO 0128996 . |
| 中间体序号 | 中间体编号 | 品名 | CAS号 | 分子式 | 供应商 | 用于合成 |
|---|---|---|---|---|---|---|
| (LIX) | 55202 | tert-butyl (4R)-4-{[methoxy(methyl)amino]carbonyl}-2,2-dimethyl-1,3-oxazolidine-3-carboxylate | C13H24N2O5 | 详情 | 详情 | |
| (LX) | 53638 | allyl(chloro)magnesium | 2622-05-1 | C3H5ClMg | 详情 | 详情 |
| (LXI) | 55203 | tert-butyl (4R)-4-(3-butenoyl)-2,2-dimethyl-1,3-oxazolidine-3-carboxylate | C14H23NO4 | 详情 | 详情 | |
| (LXII) | 55204 | tert-butyl (4R)-4-[(1S)-1-hydroxy-1-methyl-3-butenyl]-2,2-dimethyl-1,3-oxazolidine-3-carboxylate | C15H27NO4 | 详情 | 详情 | |
| (LXIII) | 55205 | tert-butyl (4R)-4-[(1S)-1-methoxy-1-methyl-3-butenyl]-2,2-dimethyl-1,3-oxazolidine-3-carboxylate | C16H29NO4 | 详情 | 详情 | |
| (LXIV) | 55206 | tert-butyl (1R,2S)-1-(hydroxymethyl)-2-methoxy-2-methyl-4-pentenylcarbamate | C13H25NO4 | 详情 | 详情 | |
| (LXV) | 55207 | tert-butyl (1R,2S)-1-(hydroxymethyl)-2-methoxy-2-methylpentylcarbamate | C13H27NO4 | 详情 | 详情 | |
| (LXVI) | 55208 | tert-butyl (1S,2S)-1-formyl-2-methoxy-2-methylpentylcarbamate | C13H25NO4 | 详情 | 详情 | |
| (LXVII) | 55209 | 1-[(hydroxyamino)methyl]-4-methoxybenzene; N-(4-methoxybenzyl)hydroxylamine | C8H11NO2 | 详情 | 详情 | |
| (LXVIII) | 55210 | {(Z,2R,3S)-2-[(tert-butoxycarbonyl)amino]-3-methoxy-3-methylhexylidene}(4-methoxybenzyl)ammoniumolate | C21H34N2O5 | 详情 | 详情 |
合成路线2
该中间体在本合成路线中的序号：(II)The protected serine derivative (I) is converted into the corresponding Weinreb amide (II) upon coupling with N,O-dimethyl hydroxylamine in the presence of CBr4/PPh3. Reaction of (II) with 4-(benzyloxy)phenylmagnesium iodide (III) affords ketone (IV). Subsequent acidic cleavage of the protecting groups of (IV) leads to the hydroxy amino ketone (V). This is then acylated by oleoyl chloride (VI) to furnish amide (VII). Phosphitylation of the primary alcohol group of (VII) with di-tert-butyl N,N-diisopropylphosphoramidite, followed by oxidation with H2O2 gives rise to phosphate ester (VIII). The tert-butyl groups of (VIII) are finally cleaved by means of trifluoroacetic acid in CH2Cl2 to provide the title compound.
| 【1】 Heasley, B.H.; MacDonald, T.L.; Lynch, K.R.; Synthesis and biological evaluation of lysophosphatidic acid (LPA) antagonists. 225th ACS Natl Meet (March 23 2003, New Orleans) 2003, Abst MEDI 248. |
| 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) | 64236 | (4S)-3-(tert-butoxycarbonyl)-2,2-dimethyl-1,3-oxazolidine-4-carboxylic acid | C11H19NO5 | 详情 | 详情 | |
| (II) | 55202 | tert-butyl (4R)-4-{[methoxy(methyl)amino]carbonyl}-2,2-dimethyl-1,3-oxazolidine-3-carboxylate | C13H24N2O5 | 详情 | 详情 | |
| (III) | 64237 | [4-(benzyloxy)phenyl](iodo)magnesium | C13H11IMgO | 详情 | 详情 | |
| (IV) | 64238 | tert-butyl (4S)-4-[4-(benzyloxy)benzoyl]-2,2-dimethyl-1,3-oxazolidine-3-carboxylate | C24H29NO5 | 详情 | 详情 | |
| (V) | 64239 | (2S)-2-amino-1-[4-(benzyloxy)phenyl]-3-hydroxy-1-propanone | C16H17NO3 | 详情 | 详情 | |
| (VI) | 28280 | Oleoyl chloride; (E)-9-Octadecenoyl chloride | C18H33ClO | 详情 | 详情 | |
| (VII) | 64240 | (Z)-N-[(1S)-2-[4-(benzyloxy)phenyl]-1-(hydroxymethyl)-2-oxoethyl]-9-octadecenamide | C34H49NO4 | 详情 | 详情 | |
| (VIII) | 64241 | (2S)-3-[4-(benzyloxy)phenyl]-2-[(Z)-9-octadecenoylamino]-3-oxopropyl di(tert-butyl) phosphate | C42H66NO7P | 详情 | 详情 |