• English
  • 简体中文
Login Register
Current Location: Home > Feedback Help Print

【结 构 式】

【分子编号】34678

【品名】3-[(4-methoxyphenyl)sulfanyl]-3-methylbutyric acid

【CA登记号】

【 分 子 式 】C12H16O3S

【 分 子 量 】240.32324

【元素组成】C 59.97% H 6.71% O 19.97% S 13.34%

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:(III)

Addition of 3-methyl-2-butenoic acid (II) to 4-methoxythiophenol (I) in the presence of piperidine at 105 C afforded adduct (III). After conversion of (III) to the corresponding acid chloride (IV) with oxalyl chloride, Friedel-Crafts cyclization using SnCl4 produced thiochromanone (V). Cleavage of the methyl ether of (V) by means of BBr3 gave phenol (VI), which was converted to triflate (VII) with trifluoromethanesulfonic anhydride in pyridine. Coupling of (VII) with trimethylsilyl acetylene (VIII) using a palladium catalyst provided (IX). Subsequent desilylation of (IX) with K2CO3 in MeOH, followed by palladium-catalyzed coupling of the resulting alkyne with ethyl 4-iodobenzoate (X) afforded the diaryl acetylene (XI). Introduction of the 4-aryl group in (XI) was achieved by conversion of (XI) to vinyl triflate (XIII) upon treatment of the sodium enolate with the bis-triflimide reagent (XII), and further condensation with 4-ethyl-phenylzinc chloride (XIV) yielding (XV). Finally, basic hydrolysis of the ethyl ester (XV) furnished the target carboxylic acid.

1 Standeven, A.M.; Escobar, M.; Wang, L.; Johnson, A.T.; Chandraratna, R.A.S.; Synthesis and biological activity of high-affinity retinoic acid receptor antagonists. Bioorg Med Chem 1999, 7, 1321.
2 Klein, E.S.; Chandraratna, R.A.; Teng, M.; Duong, T.T.; Gillett, S.J.; Beard, R.L.; Vuligonda, V.; Johnson, A.T.; Standeven, A.M.; Nagpal, S. (Allergan, Inc.); Benzopyran and benzothiopyran derivs. having retinoid antagonist-like activity. WO 9933821 .
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) 25639 4-methoxyphenylhydrosulfide; 4-methoxybenzenethiol 34320-82-6 C7H8OS 详情 详情
(II) 34677 3-methyl-2-butenoic acid 541-47-9 C5H8O2 详情 详情
(III) 34678 3-[(4-methoxyphenyl)sulfanyl]-3-methylbutyric acid C12H16O3S 详情 详情
(IV) 34679 3-[(4-methoxyphenyl)sulfanyl]-3-methylbutanoyl chloride C12H15ClO2S 详情 详情
(V) 34680 6-methoxy-2,2-dimethyl-2,3-dihydro-4H-thiochromen-4-one C12H14O2S 详情 详情
(VI) 34681 6-hydroxy-2,2-dimethyl-2,3-dihydro-4H-thiochromen-4-one C11H12O2S 详情 详情
(VII) 34682 2,2-dimethyl-4-oxo-3,4-dihydro-2H-thiochromen-6-yl trifluoromethanesulfonate C12H11F3O4S2 详情 详情
(VIII) 23897 ethynyl(trimethyl)silane;trimethylsilyl acetylene 1066-54-2 C5H10Si 详情 详情
(IX) 34683 2,2-dimethyl-6-[2-(trimethylsilyl)ethynyl]-2,3-dihydro-4H-thiochromen-4-one C16H20OSSi 详情 详情
(X) 23796 ethyl 4-iodobenzoate 51934-41-9 C9H9IO2 详情 详情
(XI) 34684 ethyl 4-[2-(2,2-dimethyl-4-oxo-3,4-dihydro-2H-thiochromen-6-yl)ethynyl]benzoate C22H20O3S 详情 详情
(XII) 34685 N-(5-chloro-2-pyridinyl)(trifluoro)-N-[(trifluoromethyl)sulfonyl]methanesulfonamide 145100-51-2 C7H3ClF6N2O4S2 详情 详情
(XIII) 34686 ethyl 4-[2-(2,2-dimethyl-4-[[(trifluoromethyl)sulfonyl]oxy]-2H-thiochromen-6-yl)ethynyl]benzoate C23H19F3O5S2 详情 详情
(XIV) 34687 chloro(4-ethylphenyl)zinc C8H9ClZn 详情 详情
(XV) 34688 ethyl 4-[2-[4-(4-ethylphenyl)-2,2-dimethyl-2H-thiochromen-6-yl]ethynyl]benzoate C30H28O2S 详情 详情
Extended Information