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【结 构 式】

【分子编号】38977

【品名】2-hydroxy-2-(2-methylphenyl)acetic acid

【CA登记号】

【 分 子 式 】C9H10O3

【 分 子 量 】166.1766

【元素组成】C 65.05% H 6.07% O 28.88%

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:(IV)

The title compound has been prepared by two related ways. The alkylation of 2-fluoro-4-hydroxybenzonitrile (I) with 3,4-(methylenedioxy)benzyl chloride (II) afforded ether (III). This was coupled with (R,S)-2-hydroxy-2-(2-methylphenyl)acetic acid (IV) in the presence of NaH in DMSO to produce the racemic adduct (V). Resolution was then achieved by fractional crystallization of the diastereoisomeric salts with (-)-ephedrine to furnish the desired (S)-enantiomer, which was finally isolated as the corresponding sodium salt.

1 Astles, P.C.; Brown, T.J.; Halley, F.; et al.; Selective ETA antagonists. 5. Discovery and structure-activity relationships of phenoxyphenylacetic acid derivatives. J Med Chem 2000, 43, 5, 900.
2 Porter, B.; Astles, P.C.; Bridge, A.W.; McLay, I.M.; Van Sickle, A.P.; Walsh, R.J.A.; McCarthy, C.; Morley, A.D.; Halley, F.; Harris, N.V.; Majid, T.N.; Smith, C. (Rhône-Poulenc Rorer Ltd.); Substd. phenyl cpds. as endothelin antagonists. US 6048893; US 6124343; WO 9622978 .
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) 20094 2,4-dihydroxybenzaldehyde 95-01-2 C7H6O3 详情 详情
(II) 28617 5-(chloromethyl)-1,3-benzodioxole C8H7ClO2 详情 详情
(III) 38975 (3S,5R)-1-[(2S,4R)-5-[(3aS,8aR)-2,2-dimethyl-8,8a-dihydro-2H-indeno[1,2-d][1,3]oxazol-3(3aH)-yl]-4-benzyl-2-hydroxy-5-oxopentyl]-3,5-dibenzyl-2-pyrrolidinone C42H46N2O4 详情 详情
(IV) 38977 2-hydroxy-2-(2-methylphenyl)acetic acid C9H10O3 详情 详情
(V) 38978 2-[5-(1,3-benzodioxol-5-ylmethoxy)-2-cyanophenoxy]-2-(2-methylphenyl)acetic acid C24H19NO6 详情 详情

合成路线2

该中间体在本合成路线中的序号:(IV)

The alkylation of 2-fluoro-4-hydroxybenzonitrile (I) with 4-picolyl chloride (II) afforded ether (III). This was coupled with (R,S)-2-hydroxy-2-(2-methylphenyl)acetic acid (IV) in the presence of NaH in DMSO to produce the racemic adduct (V). Resolution of (V) was then achieved by fractional crystallization of the diastereoisomeric salts with (-)-ephedrine to furnish the desired (S)-enantiomer, which was finally isolated as the corresponding sodium salt.

1 Astles, P.C.; Brown, T.J.; Halley, F.; et al.; Selective ETA antagonists. 5. Discovery and structure-activity relationships of phenoxyphenylacetic acid derivatives. J Med Chem 2000, 43, 5, 900.
2 Porter, B.; Astles, P.C.; Bridge, A.W.; McLay, I.M.; Van Sickle, A.P.; Walsh, R.J.A.; McCarthy, C.; Morley, A.D.; Halley, F.; Harris, N.V.; Majid, T.N.; Smith, C. (Rhône-Poulenc Rorer Ltd.); Substd. phenyl cpds. as endothelin antagonists. US 6048893; US 6124343; WO 9622978 .
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) 20094 2,4-dihydroxybenzaldehyde 95-01-2 C7H6O3 详情 详情
(II) 10844 4-(Chloromethyl)pyridine 10445-91-7 C6H6ClN 详情 详情
(III) 38985 2-fluoro-4-(4-pyridinylmethoxy)benzonitrile C13H9FN2O 详情 详情
(IV) 38977 2-hydroxy-2-(2-methylphenyl)acetic acid C9H10O3 详情 详情
(V) 38986 2-[2-cyano-5-(4-pyridinylmethoxy)phenoxy]-2-(2-methylphenyl)acetic acid C22H18N2O4 详情 详情
Extended Information