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

【结 构 式】

【分子编号】20240

【品名】2-(2,4,6-triisopropylphenyl)acetic acid

【CA登记号】

【 分 子 式 】C17H26O2

【 分 子 量 】262.39224

【元素组成】C 77.82% H 9.99% O 12.2%

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:(V)

1) Synthesis of intermediate (V): The reduction of 2,4,6-triisopropylbenzoyl chloride (I) with LiAlH4 in ethyl ether gives 2,4,6-triisopropylbenzyl alcohol (II) (1-4), which by reaction with SOCl2 in toluene is converted into 2,4,6-triisopropylbenzyl chloride (III). The reaction of (III) with NaCN or KCN in DMSO affords 2,4,6-triisopropylphenylacetonitrile (IV), which is hydrolyzed with aqueous H2SO4 or KOH in diethylene glycol/water, yielding the phenylacetic acid (V). 2) Synthesis of intermediate (III): The intermediate benzyl chloride (III) can also be obtained by direct chloromethylation of 1,3,5-triisopropylbenzene (XI) with paraformaldehyde/HCl in acetic acid. 3) Synthesis of intermediate (V): Phenylacetic acid (V) can also be obtained by condensation of 1,3,5-triisopropylbenzene (XI) with glyoxylic acid (XIV) by means of H2SO4 in refluxing acetic acid, yielding a mixture of acetoxyacetic acid (XV) and hydroxyacetic acid (XVI). This mixture is finally reduced with HI in acetic acid to the phenylacetic acid (V). 4) Synthesis of intermediate (IV): The acetonitrile (IV) can also be obtained by reaction of benzyl bromide (XII) with KCN in DMSO. 5) Synthesis of intermediate (XIII): Avasimibe can also be obtained by reaction of benzyl alcohol (II) with PBr3 in ether to give the benzyl bromide (XII), which is treated with Mg in THF to yield the corresponding Grignard reagent (XIII).

1 Sliskovic, D.R.; CI-1011: An atypical ACAT inhibitor with antiatherosclerotic activity. Int Symp Med Chem 1996, Abst SR-06.2.
2 Lee, H.T.; Sliskovic, D.R.; Picard, J.A.; et al.; Inhibitors of acyl-CoA:cholesterol O-acyl transferase (ACAT) as hypocholesterolemic agents. CI-1011: An acyl sulfamate with unique cholesterol-lowering activity in animals fed noncholesterol-supplemented diets. J Med Chem 1996, 39, 26, 5031.
3 Sorbera, L.A.; Rabasseda, X.; Castañer, J.; Avasimibe . Drugs Fut 1999, 24, 1, 9.
4 Lee, H.T.; Picad, J.A.; Sliskovic, D.R.; Wierenga, W. (Pfizer Inc.); N-Acyl sulfamic acid esters (or thioesters), N-acyl sulfonamides, and N-sulfonyl carbamic acid esters (or thioesters) as hypercholesterolemic agents. EP 0698010; JP 1996510256; US 5491172; WO 9426702 .
5 Dozeman, G.J.; et al.; Chemical development of a pilot scale process for the ACAT inhibitor 2,6-diisopropylphenyl [(2,4,6-triisopropylphenyl)acetyl]sulfamate. Org Process Res Dev 1997, 1, 2, 137-48.
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) 20236 2,4,6-triisopropylbenzoyl chloride 57199-00-5 C16H23ClO 详情 详情
(II) 20237 (2,4,6-triisopropylphenyl)methanol C16H26O 详情 详情
(III) 20238 2-(chloromethyl)-1,3,5-triisopropylbenzene C16H25Cl 详情 详情
(IV) 20239 2-(2,4,6-triisopropylphenyl)acetonitrile C17H25N 详情 详情
(V) 20240 2-(2,4,6-triisopropylphenyl)acetic acid C17H26O2 详情 详情
(XI) 14888 1,3,5-triisopropylbenzene 717-74-8 C15H24 详情 详情
(XII) 20242 2-(bromomethyl)-1,3,5-triisopropylbenzene C16H25Br 详情 详情
(XIII) 20243 bromo(2,4,6-triisopropylbenzyl)magnesium C16H25BrMg 详情 详情
(XIV) 15168 methyl 2-chloro-2-fluorocyclopropanecarboxylate C5H6ClFO2 详情 详情
(XV) 20245 2-(acetoxy)-2-(2,4,6-triisopropylphenyl)acetic acid C19H28O4 详情 详情
(XVI) 20246 2-hydroxy-2-(2,4,6-triisopropylphenyl)acetic acid C17H26O3 详情 详情

合成路线2

该中间体在本合成路线中的序号:(V)

1) The reaction of (V) with SOCl2 or (COCl)2 in DMF affords the expected acyl chloride (VI), which is finally condensed with 2,6-diisopropylphenyl sulfamate (VII) by means of triethylamine in hot toluene to obtain Avasimibe. 2) The sulfamate (VII) can be obtained by condensation of 2,6-diisopropylphenol (VIII) with chlorosulfonyl isocyanate (IX) in refluxing toluene to give the isocyanate (X), which is hydrolyzed with water to the sulfamate (VII). compound is condensed with the previously described isocyanate (X) in refluxing THF to obtain Avasimibe. 3) Avasimibe can also be obtained by condensation of isocyanate (X) with Grignard reagent (XIII).

1 Sorbera, L.A.; Rabasseda, X.; Castañer, J.; Avasimibe . Drugs Fut 1999, 24, 1, 9.
2 Lee, H.T.; Picad, J.A.; Sliskovic, D.R.; Wierenga, W. (Pfizer Inc.); N-Acyl sulfamic acid esters (or thioesters), N-acyl sulfonamides, and N-sulfonyl carbamic acid esters (or thioesters) as hypercholesterolemic agents. EP 0698010; JP 1996510256; US 5491172; WO 9426702 .
中间体序号 中间体编号 品名 CAS号 分子式 供应商 用于合成
(V) 20240 2-(2,4,6-triisopropylphenyl)acetic acid C17H26O2 详情 详情
(VI) 20247 2-(2,4,6-triisopropylphenyl)acetyl chloride C17H25ClO 详情 详情
(VII) 20248 2,6-diisopropylphenylsulfamate C12H19NO3S 详情 详情
(VIII) 20249 2,6-Diisopropylphenol 2078-54-8 C12H18O 详情 详情
(IX) 14101 Chlorosulfonyl isocyanate 1189-71-5 CClNO3S 详情 详情
(X) 20251 2-[(isocyanatosulfonyl)oxy]-1,3-diisopropylbenzene C13H17NO4S 详情 详情
(XIII) 20243 bromo(2,4,6-triisopropylbenzyl)magnesium C16H25BrMg 详情 详情
Extended Information