【结 构 式】 |
【分子编号】43325 【品名】3,4-difluorobenzylamine; (3,4-difluorophenyl)methanamine 【CA登记号】72235-53-1 |
【 分 子 式 】C7H7F2N 【 分 子 量 】143.1361264 【元素组成】C 58.74% H 4.93% F 26.55% N 9.79% |
合成路线1
该中间体在本合成路线中的序号:(X)In an alternative procedure, 3,4-difluorobenzylamine (X) was condensed with benzophenone in the presence of a catalytic amount of boron trifluoride etherate to afford imine (XI). After deprotonation of (XI) with tert-butyllithium, its condensation with acetaldehyde produced a protected amino alcohol, which was then deprotected by treatment with O-methyl hydroxylamine. The resulting amino alcohol (VI) was converted to oxazolidine (IX) by the same method as above.
【1】 Tian, D.; Jeon, Y.; Lagu, B.; et al.; De novo design of a novel oxazolidinone analogue as a potent and selective alpha1A adrenergic receptor antagonist with high oral bioavailability. J Med Chem 2000, 43, 15, 2775. |
中间体序号 | 中间体编号 | 品名 | CAS号 | 分子式 | 供应商 | 用于合成 |
---|---|---|---|---|---|---|
(VI) | 43321 | 1-amino-1-(3,4-difluorophenyl)-2-propanol | C9H11F2NO | 详情 | 详情 | |
(X) | 43325 | 3,4-difluorobenzylamine; (3,4-difluorophenyl)methanamine | 72235-53-1 | C7H7F2N | 详情 | 详情 |
(XI) | 43326 | N-(3,4-difluorobenzyl)-N-(dibenzylene)amine; (3,4-difluorophenyl)-N-(dibenzylene)methanamine | C20H15F2N | 详情 | 详情 |
合成路线2
该中间体在本合成路线中的序号:(XII)The reaction of (S)-(+)-methyl lactate (I) with pyrrolidine (II) gives the corresponding acyl pyrrolidine (III), which is silylated with Tbdms-Cl and imidazole to yield the silyl ether (IV). The condensation of (IV) with 3,4-difluorobromobenzene (V) by means of BuLi in THF affords the chiral propiophenone derivative (VI), which is treated with hydroxylamine and NaOAc in methanol to provide the corresponding oxime (VII). The reduction of (VII) with LiAlH4 in refluxing ethyl ether gives the expected amine (VIII), which is treated with (Boc)2O in chloroform, yielding the carbamate (IX). The cyclization of (IX) by means of NaH in THF gives a mixture of cis- and trans-oxazolidinones, from which the desired trans-(4S,5S)-isomer (X) is separated by flash chromatography. The reaction of (X) with 4-nitrophenyl chloroformate (XI) by means of NaH yields the oxazolidinone-carboxylate (XII), which is finally condensed with 3-[4-(4-fluorophenyl)piperidin-1-yl]propylamine (XIII) in THF to afford the target amide.
【1】 Lagu, B.; Wetzel, J.M.; Forray, C.; Patane, M.A.; Bock, M.G.; Determination of the relative and absolute stereochemistry of a potent and alpha1A-selective adrenoceptor antagonist. Bioorg Med Chem Lett 2000, 10, 24, 2705. |
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) | 17075 | propionic acid, 2-hydroxy-, methyl ester, (S)-; methyl (2S)-2-hydroxypropanoate | 27871-49-4 | C4H8O3 | 详情 | 详情 |
(II) | 11376 | Pyrrolidine | 123-75-1 | C4H9N | 详情 | 详情 |
(III) | 17099 | (2S)-2-hydroxy-1-(1-pyrrolidinyl)-1-propanone | C7H13NO2 | 详情 | 详情 | |
(IV) | 51565 | (2S)-2-[[tert-butyl(dimethyl)silyl]oxy]-1-(1-pyrrolidinyl)-1-propanone | C13H27NO2Si | 详情 | 详情 | |
(V) | 51566 | 1-Bromo-3,4-difluorobenzene; 3,4-Difluorobromobenzene; 4-Bromo-1,2-difluorobenzene | 348-61-8 | C6H3BrF2 | 详情 | 详情 |
(VI) | 51567 | (2S)-2-[[tert-butyl(dimethyl)silyl]oxy]-1-(3,4-difluorophenyl)-1-propanone | C15H22F2O2Si | 详情 | 详情 | |
(VII) | 51568 | (2S)-2-[[tert-butyl(dimethyl)silyl]oxy]-1-(3,4-difluorophenyl)-1-propanone oxime | C15H23F2NO2Si | 详情 | 详情 | |
(VIII) | 51569 | (2S)-1-amino-1-(3,4-difluorophenyl)-2-propanol | C9H11F2NO | 详情 | 详情 | |
(IX) | 51570 | tert-butyl (2S)-1-(3,4-difluorophenyl)-2-hydroxypropylcarbamate | C14H19F2NO3 | 详情 | 详情 | |
(X) | 43324 | (4S,5S)-4-(3,4-difluorophenyl)-5-methyl-1,3-oxazolidin-2-one | C10H9F2NO2 | 详情 | 详情 | |
(XI) | 16605 | 4-Nitrophenyl chloroformate; 1-[(Chlorocarbonyl)oxy]-4-nitrobenzene | 7693-46-1 | C7H4ClNO4 | 详情 | 详情 |
(XII) | 43325 | 3,4-difluorobenzylamine; (3,4-difluorophenyl)methanamine | 72235-53-1 | C7H7F2N | 详情 | 详情 |
(XIII) | 39302 | 3-[4-(4-fluorophenyl)-1-piperidinyl]propylamine; 3-[4-(4-fluorophenyl)-1-piperidinyl]-1-propanamine | C14H21FN2 | 详情 | 详情 |