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【结 构 式】

【分子编号】13299

【品名】3-Bromopropionic acid potassium salt

【CA登记号】

【 分 子 式 】C3H4BrKO2

【 分 子 量 】191.06586

【元素组成】C 18.86% H 2.11% Br 41.82% K 20.46% O 16.75%

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)

A new synthesis of MK-417 has been published: The reaction of thiophene (I) with butyllithium and sulfur in THF yields thiophene-2-thiol lithium salt (II) which, without isolation, is condensed with potassium 3-bromopropionate (III) in water - THF giving 3-(2-thienylthio)propanoic acid (IV). The cyclization of (IV) with trifluoroacetic anhydride in hot toluene affords 5,6-dihydro-4H-thieno[2,3-b]thiopyran-4-one (V), which is oxidized with H2O2 and sodium tungstate in ethyl acetate - toluene to give the corresponding 7,7-dioxide (VI). The stereocontrolled reduction of (VI) with borane - methylsulfide and (S)-1-methyl-3,3-diphenyltetrahydropyrrolo[1,2-c][1,3,2]oxaazaborole as catalyst in THF yields (R)-(+)-5,6-dihydro-4H-thieno[2,3-b]thiopyran-4-ol 7,7-dioxide (VII), which is converted to the corresponding sodium salt (VIII) with sodium acetylide in THF. This salt (VIII), without isolation, is treated with p-toluenesulfonyl chloride to afford the corresponding tosylate (IX) which, also without isolation, is condensed with isobutylamine (X) to give (S)-(-)-4-(2-methylpropylamino)-5,6-dihydro-4H-thieno[2,3-b]thiopyran 7,7-dioxide (XI). The reaction of (XI), first with oleum and then with thionyl chloride, yields the corresponding 2-sulfonyl chloride (XII), which is finally treated with aqueous ammonium hydroxide.

1 Reamer, R.A.; Jones, T.J.; Jones, E.T.T.; Blacklock, T.J.; Grabowski, E.J.J.; Mathre, D.J.; Roberts, F.E.; Mohan, J.J.; Xavier, L.C.; Sohar, P.; An asymmetric synthesis of MK-0417 - Observations on oxazaborolidine-catalyzed reductions. J Org Chem 1991, 56, 2, 763.
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) 13297 Thiophene 110-02-1 C4H4S 详情 详情
(II) 13298 2-Sulfanylthiophene lithium salt C4H3LiS2 详情 详情
(III) 13299 3-Bromopropionic acid potassium salt C3H4BrKO2 详情 详情
(IV) 13300 3-(2-Thienylsulfanyl)propionic acid C7H8O2S2 详情 详情
(V) 13301 5,6-Dihydro-4H-thieno[2,3-b]thiopyran-4-one C7H6OS2 详情 详情
(VI) 13302 2,3-Dihydro-2H-thieno[2,3-b]thiopyran-1,1,4-trione C7H6O3S2 详情 详情
(VII) 13303 (4R)-4-Hydroxy-3,4-dihydro-2H-thieno[2,3-b]thiopyran-1,1(2H)-dione C7H8O3S2 详情 详情
(VIII) 13304 sodium (4R)-1,1-dioxo-1,2,3,4-tetrahydro-2H-thieno[2,3-b]thiopyran-4-olate C7H7NaO3S2 详情 详情
(IX) 13305 (4R)-1,1-dioxo-1,2,3,4-tetrahydro-2H-thieno[2,3-b]thiopyran-4-yl 4-methylbenzenesulfonate C14H14O5S3 详情 详情
(X) 13306 2-Methyl-1-propanamine; Isobutylamine 78-81-9 C4H11N 详情 详情
(XI) 13307 (4S)-4-(Isobutylamino)-3,4-dihydro-2H-thieno[2,3-b]thiopyran-1,1(2H)-dione C11H17NO2S2 详情 详情
(XII) 13308 (4S)-4-(Isobutylamino)-1,1-dioxo-1,2,3,4-tetrahydro-2H-thieno[2,3-b]thiopyran-6-sulfonyl chloride C11H16ClNO4S3 详情 详情
Extended Information