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【结 构 式】

【分子编号】69354

【品名】cyclobutanemethanol;Cyclobutylcarbinol;Hydroxymethylcyclobutane

【CA登记号】4415-82-1

【 分 子 式 】C5H10O

【 分 子 量 】 86.1338

【元素组成】C 69.72% H 11.7% O 18.58%

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:(XXVIII)

Oxidation of cyclobutanemethanol (XXVIII) with NaOCl and catalytic TEMPO by means of KBr and NaHCO3 in CH2Cl2/H2O gives cyclobutanecarboxaldehyde (XXIX), which is then condensed with nitromethane in the presence of Et3N in toluene to yield the nitro alcohol (XXX). Subsequent treatment of alcohol (XXX) with acetic anhydride in the presence of DMAP furnishes a mixture of the acetate ester (XXXI) and the dehydration compound (2-nitrovinyl)cyclobutane (XXXII), which can also be obtained as the only reaction product by dehydration of nitro alcohol (XXX) with MsCl in the presence of Et3N. Reduction of the mixture of compounds (XXXI) and (XXXII) or the nitro olefin (XXXII) by catalytic hydrogenation over Pd/C in MeOH optionally in the presence of Et3N, or with NaBH4 in PEG-400/H2O or t-BuOH, affords (2-nitroethyl)cyclobutane (XXXIII), which is condensed with glyoxylic acid (XXXIV) in the presence of Et3N to yield the nitro hydroxy acid (XXXV). Then, compound (XXXV) is reduced with H2 over Pd/C in MeOH and esterified with MeOH and p-TsOH·H2O to give amino ester (XXXVI). Finally, aminolysis of methyl ester (XXXVI) with NH3 and NH4OH in MeOH followed by N-protection by means of Boc2O and K2CO3 in MeOH/H2O yields intermediate (XXVII) .

1 Park, J., Vater, E.J., Dong, S., Iwama, T., Raghavan, R.R., Lee, H.-C.,Wong, G.S.K. (Schering Corp.). Preparation of 3-amino-3-(cyclobutylmethyl)-2-(hydroxy)-propionamide hydrochloride. CA 2672570, WO 2008082486.
中间体序号 中间体编号 品名 CAS号 分子式 供应商 用于合成
(XXVII) 69353 tert-butyl (4-amino-1-cyclobutyl-3-hydroxy-4-oxobutan-2-yl)carbamate C13H24N2O4 详情 详情
(XXVIII) 69354 cyclobutanemethanol;Cyclobutylcarbinol;Hydroxymethylcyclobutane 4415-82-1 C5H10O 详情 详情
(XXIX) 69355 cyclobutanecarbaldehyde;Cyclobutanaldehyde;Cyclobutylcarboxaldehyde;Formylcyclobutane 2987-17-9 C5H8O 详情 详情
(XXX) 69356 1-cyclobutyl-2-nitroethanol C6H11NO3 详情 详情
(XXXI) 69357 1-cyclobutyl-2-nitroethyl acetate C8H13NO4 详情 详情
(XXXII) 69358 (E)-(2-nitrovinyl)cyclobutane C6H9NO2 详情 详情
(XXXIII) 69359 (2-nitroethyl)cyclobutane C6H11NO2 详情 详情
(XXXIV) 15618 2-Oxoacetic acid; Glyoxylic Acid 298-12-4 C2H2O3 详情 详情
(XXXV) 69360 4-cyclobutyl-2-hydroxy-3-nitrobutanoic acid C8H13NO5 详情 详情
(XXXVI) 69361 methyl 3-amino-4-cyclobutyl-2-hydroxybutanoate 4-methylbenzenesulfonate C9H17NO3.C7H8O3S 详情 详情
Extended Information