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【结 构 式】

【分子编号】20610

【品名】methyl (2R)-4-amino-6-fluoro-2-methyl-3,4-dihydro-2H-chromene-4-carboxylate

【CA登记号】

【 分 子 式 】C12H14FNO3

【 分 子 量 】239.2465032

【元素组成】C 60.24% H 5.9% F 7.94% N 5.85% O 20.06%

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:(X)

2) The condensation of 4-fluorophenol (I) with ethyl (S)-lactate (II) by means of diethyl azodicarboxylate and triphenylphosphine in THF gives ethyl 2(R)-(4-fluorophenoxy)propionate (III), which is reduced with LiAlH4 in THF yielding 2(R)-(4-fluorophenoxy)propanol (IV). The reaction of (IV) with Br2 and triphenylphosphine in DMF affords 1-bromo-2(R)-(4-fluorophenoxy)propane (V), which is condensed with N-benzoyl-2-hydroxyglycine (VI) by means of methanesulfonic acid to give (RS)-N-benzoyl-2-[2-(1-bromo-2(R)propoxy)-5-fluorophenyl]glycine (VII). The cyclization of (VII) by means of acetic anhydride and K2CO3 in acetone yields 6-fluoro-2(R)-methyl-2'-phenylspiro[2,3-dihydro-4H-1-benzopyran-4(RS),4'-oxazolidin]-5'-one (VIII), which is hydrolyzed with refluxing formic acid-HCl affording 4(RS)-amino-6-fluoro-2(R)-methyl-2,3-dihydro-4H-1-benzopyran-4-carboxylic acid (IX). The esterification of (IX) with Cl2SO and methanol gives the corresponding methyl ester (X), which is submitted to optical resolution with alpha-chymotrypsine to yield methyl 4(S)-amino-6-fluoro-2(R)-methyl-2,3-dihydro-4H-1-benzopyran-4-carboxylate (XI). Finally, this compound is cyclized with sodium cyanate in acetic acid.

1 Prous, J.; Castaner, J.; METHOSORBINIL. Drugs Fut 1989, 14, 4, 325.
2 Moore, B.S.; Urban, F.J.; Dirlam, N.L.; Novel synthesis of the aldose reductase inhibitor sorbinil via amidoalkylation, intramolecular oxazolidin-5-one alkylation, and chymotrypsin resolution. J Org Chem 1987, 52, 16, 3587.
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) 19639 4-fluorophenol 371-41-5 C6H5FO 详情 详情
(II) 16659 ethyl (2S)-2-hydroxypropanoate; (S)-ethyl lactate 687-47-8 C5H10O3 详情 详情
(III) 20603 ethyl (2R)-2-(4-fluorophenoxy)propanoate C11H13FO3 详情 详情
(IV) 20604 (2R)-2-(4-fluorophenoxy)-1-propanol C9H11FO2 详情 详情
(V) 20605 1-[[(1R)-2-bromo-1-methylethyl]oxy]-4-fluorobenzene; (1R)-2-bromo-1-methylethyl 4-fluorophenyl ether C9H10BrFO 详情 详情
(VI) 20606 2-(benzoylamino)-2-hydroxyacetic acid 16555-77-4 C9H9NO4 详情 详情
(VII) 20607 2-(benzoylamino)-2-(2-[[(1R)-2-bromo-1-methylethyl]oxy]-5-fluorophenyl)acetic acid C18H17BrFNO4 详情 详情
(VIII) 20608 6-Fluoro-2(R)-methyl-2'-phenyl-3,4,4',5'-tetrahydro-2H-spiro[1-benzopyran-4,4'-oxazol]-5'-one C18H14FNO3 详情 详情
(IX) 20609 (2R)-4-amino-6-fluoro-2-methyl-3,4-dihydro-2H-chromene-4-carboxylic acid C11H12FNO3 详情 详情
(X) 20610 methyl (2R)-4-amino-6-fluoro-2-methyl-3,4-dihydro-2H-chromene-4-carboxylate C12H14FNO3 详情 详情
(XI) 20611 (2R,4S)-4-amino-6-fluoro-2-methyl-3,4-dihydro-2H-chromene-4-carboxylic acid C11H12FNO3 详情 详情
Extended Information