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【结 构 式】

【分子编号】21156

【品名】ethyl 3-hydroxy-3-phenethylhexanoate

【CA登记号】

【 分 子 式 】C16H24O3

【 分 子 量 】264.36476

【元素组成】C 72.69% H 9.15% O 18.16%

与该中间体有关的原料药合成路线共 2 条

合成路线1

该中间体在本合成路线中的序号:(II)

1) The condensation of 1-phenylhexan-3-one (I) with ethyl acetate by means of butyllithium and diisopropylamine in THF gives racemic 3-hydroxy-3-(2-phenylethyl)hexanoic acid ethyl ester (II), which is hydrolyzed with NaOH in methanol to the corresponding free acid (III). The optical resolution of (III) with (1R,2S)-(-)-norephedrine (IV) followed by treatment with aqueous HCl yields the chiral (R)-acid (V), which is treated with 4-biphenylyloxymethyl chloride (VI) and diisopropylethylamine in toluene affording the protected ester (VII). The reduction of the ester group of (VII) with diisobutylaluminum hydride (DIBAL) in toluene gives the monoprotected diol (VIII), which is oxidized at the primary hydroxy group with 4-hydroxy-2,2,6,6-tetramethylpiperidinyloxy radical (TEMPO) and NaOCl yielding the corresponding aldehyde (IX). The condensation of (IX) with (R)-3-(3-nitrophenyl)pentanoic acid methyl ester (X) by means of sodium hexamethyldisilazide (NaHMDS) in THF gives the hydroxyester (XI) as a mixture of four diastereomers. This mixture is oxidized with pyridinium chlorochromate (PCC) in dichloromethane to afford the ketoester (XII) also as a mixture of two diastereomers. Elimination of the biphenylyloxymethyl protecting group with H2SO4 in methanol yields the hydroxy ketoester (XIII).

1 Fors, K.S.; et al.; A convergent, scalable synthesis of HIV protease inhibitor PNU-140690. J Org Chem 1998, 63, 21, 7348.
中间体序号 中间体编号 品名 CAS号 分子式 供应商 用于合成
17491 ethyl acetate 141-78-6 C4H8O2 详情 详情
(I) 17233 1-phenyl-3-hexanone C12H16O 详情 详情
(II) 21156 ethyl 3-hydroxy-3-phenethylhexanoate C16H24O3 详情 详情
(III) 21157 3-hydroxy-3-phenethylhexanoic acid C14H20O3 详情 详情
(IV) 13355 2-Amino-1-phenyl-1-propanol; (1S,2R)-(+)-Norephedrine 37577-28-9 C9H13NO 详情 详情
(IV) 21158 (1R,2S)-2-amino-1-phenyl-1-propanol C9H13NO 详情 详情
(V) 21159 (3R)-3-hydroxy-3-phenethylhexanoic acid C14H20O3 详情 详情
(VI) 21160 [1,1'-biphenyl]-4-yl chloromethyl ether; 4-(chloromethoxy)-1,1'-biphenyl C13H11ClO 详情 详情
(VII) 21161 ([1,1'-biphenyl]-4-yloxy)methyl (3R)-3-[([1,1'-biphenyl]-4-yloxy)methoxy]-3-phenethylhexanoate C40H40O5 详情 详情
(VIII) 21162 (3R)-3-[([1,1'-biphenyl]-4-yloxy)methoxy]-3-phenethyl-1-hexanol C27H32O3 详情 详情
(IX) 21163 (3R)-3-[([1,1'-biphenyl]-4-yloxy)methoxy]-3-phenethylhexanal C27H30O3 详情 详情
(X) 21164 methyl (3S)-3-(3-nitrophenyl)pentanoate C12H15NO4 详情 详情
(XI) 21165 methyl (5R)-5-[([1,1'-biphenyl]-4-yloxy)methoxy]-3-hydroxy-2-[(1S)-1-(3-nitrophenyl)propyl]-5-phenethyloctanoate C39H45NO7 详情 详情
(XII) 21166 methyl (5R)-5-[([1,1'-biphenyl]-4-yloxy)methoxy]-2-[(1S)-1-(3-nitrophenyl)propyl]-3-oxo-5-phenethyloctanoate C39H43NO7 详情 详情
(XIII) 21167 methyl (5R)-5-hydroxy-2-[(1S)-1-(3-nitrophenyl)propyl]-3-oxo-5-phenethyloctanoate C26H33NO6 详情 详情

合成路线2

该中间体在本合成路线中的序号:(III)

 

1 Wilken J. Nerenz F, Kanschik-Conndsen A. 2004. A process for the synthesis of 3-hydroxy3-(2-phenylethyl) hexanoic acid,useful as an intermediate for antiviral. US 2004110957(本专利属于Honey-well International, Inc.,USA)
中间体序号 中间体编号 品名 CAS号 分子式 供应商 用于合成
(V) 21159 (3R)-3-hydroxy-3-phenethylhexanoic acid C14H20O3 详情 详情
(VII) 66860 (S)-4-hydroxy-6-phenethyl-6-propyl-5,6-dihydro-2H-pyran-2-one   C16H20O3 详情 详情
(I) 17233 1-phenyl-3-hexanone C12H16O 详情 详情
(II) 16640 Ethyl 2-bromoacetate; Ethyl bromoacetate 105-36-2 C4H7BrO2 详情 详情
(III) 21156 ethyl 3-hydroxy-3-phenethylhexanoate C16H24O3 详情 详情
(IV) 13355 2-Amino-1-phenyl-1-propanol; (1S,2R)-(+)-Norephedrine 37577-28-9 C9H13NO 详情 详情
(VI) 66856 (S)-ethyl 5-hydroxy-3-oxo-5-phenethyloctanoate   C18H26O4 详情 详情
(IX) 17236 (6R)-3-[(1R)-1-(3-aminophenyl)propyl]-4-hydroxy-6-phenethyl-6-propyl-5,6-dihydro-2H-pyran-2-one C25H31NO3 详情 详情
Extended Information