n-Butyl Chloroacetate; butyl 2-chloroacetate -Drug Synthesis Database

【结构式】

【分子编号】14595

【品名】n-Butyl Chloroacetate; butyl 2-chloroacetate

【CA登记号】590-02-3

【分子式】C₆H₁₁ClO₂

【分子量】150.60484

【元素组成】C 47.85% H 7.36% Cl 23.54% O 21.25%

与该中间体有关的原料药合成路线共 3 条

合成路线1 合成路线2 合成路线3

合成路线1

该中间体在本合成路线中的序号：(II)

2-Mercaptothiazolo[5,4-b]pyridine (I) is treated with chloroacetic acid butyl ester (II) in the presence of potassium carbonate in DMF to give 2-[(butoxycarbonylmethyl)thio]thiazolo[5,4-b]pyridine (III), which is oxidized with m-chloroperbenzoic acid in dichloromethane.

参考文献中间体

合成目标

【1】 Katano, K.; Tomomoto, T.; Ogino, H.; Yamazaki, N.; Hirano, F.; Yuda, Y.; Konno, F.; Nishio, M.; Machinami, T.; Shibahara, S.; Tsuruoka, T.; Inouye, S. (Meiji Seika Kaisha, Ltd.); Azole derivs. and antiulcerative compsn. containing same. EP 0405976; JP 1991218377; US 5079255; US 5141946; US 5200407 .
【2】 Castaner, J.; Mealy, N.; Prous, J.; ME-3407. Drugs Fut 1994, 19, 1, 31.

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)	14594	[1,3]thiazolo[5,4-b]pyridine-2-thiol; [1,3]thiazolo[5,4-b]pyridin-2-ylhydrosulfide		C₆H₄N₂S₂	详情	详情
(II)	14595	n-Butyl Chloroacetate; butyl 2-chloroacetate	590-02-3	C₆H₁₁ClO₂	详情	详情
(III)	14596	butyl 2-([1,3]thiazolo[5,4-b]pyridin-2-ylsulfanyl)acetate		C₁₂H₁₄N₂O₂S₂	详情	详情

合成路线2

该中间体在本合成路线中的序号：(II)

The condensation of 4-(tert-butoxycarbonylamino)piperidine (I) with butyl chloroacetate (II) by means of TEA in hot DMF gives butyl 2-[4-(tert-butoxycarbonylamino)piperdin-1-yl]acetate (III), which is deprotected with HCl in isopropanol to yield butyl 2-(4-aminopiperidin-1-yl)acetate (IV). Finally, this compound is condensed with 4-amino-5-chloro-2-methoxybenzoic acid (V) by means of ethyl chloroacetate, TEA and K2CO3 in THF to afford the target benzamide.

参考文献中间体

合成目标

【1】 Sakaguchi, J.; Kato, H.; Kado, N. (Hokuriku Seiyaku Co., Ltd.); Benzamide derivs. and drugs containing the same. EP 1149832; JP 2000290254; WO 0046201 .

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)	41601	tert-butyl 4-piperidinylcarbamate; 4-tert-Boc-aminopiperidine	73874-95-0	C₁₀H₂₀N₂O₂	详情	详情
(II)	14595	n-Butyl Chloroacetate; butyl 2-chloroacetate	590-02-3	C₆H₁₁ClO₂	详情	详情
(III)	51930	butyl 2-[4-[(tert-butoxycarbonyl)amino]-1-piperidinyl]acetate		C₁₆H₃₀N₂O₄	详情	详情
(IV)	51931	butyl 2-(4-amino-1-piperidinyl)acetate		C₁₁H₂₂N₂O₂	详情	详情
(V)	12419	4-Amino-5-chloro-2-methoxybenzoic acid	7206-70-4	C₈H₈ClNO₃	详情	详情

合成路线3

该中间体在本合成路线中的序号：(V)

A new synthetic route has been reported. 4-Amino-1-benzylpiperidine (I) was protected as the t-butyl carbamate (II) using Boc2O, and the N-benzyl group was subsequently removed by transfer hydrogenolysis, yielding 4-(t-butoxycarbonylamino)piperidine (III). Butyl chloroacetate (V), prepared by treatment of chloroacetyl chloride (IV) with n-butanol, was then condensed with piperidine (III) to afford (VI). After acidic cleavage of the Boc protecting group of (VI), the resultant amino piperidine (VII) was acylated with the mixed anhydride (VIII) to provide the target amide.

参考文献中间体

合成目标

【1】 Sakaguchi, J.; et al.; An improved synthesis of butyl 4-[(4-amino-5-chloro-2-methoxybenzoyl)amino]-1-piperidineacetate (AU-224). Chem Pharm Bull 2001, 49, 6, 788.

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)	34808	1-Benzyl-4-piperidinylamine; 1-Benzyl-4-piperidinamine; 4-Amino-1-benzylpiperidine	50541-93-0	C₁₂H₁₈N₂	详情	详情
(II)	56563	tert-butyl 1-benzyl-4-piperidinylcarbamate		C₁₇H₂₆N₂O₂	详情	详情
(III)	41601	tert-butyl 4-piperidinylcarbamate; 4-tert-Boc-aminopiperidine	73874-95-0	C₁₀H₂₀N₂O₂	详情	详情
(IV)	11296	2-Chloroacetyl chloride; Chloroacetic chloride	79-04-9	C₂H₂Cl₂O	详情	详情
(V)	14595	n-Butyl Chloroacetate; butyl 2-chloroacetate	590-02-3	C₆H₁₁ClO₂	详情	详情
(VI)	51930	butyl 2-[4-[(tert-butoxycarbonyl)amino]-1-piperidinyl]acetate		C₁₆H₃₀N₂O₄	详情	详情
(VII)	51931	butyl 2-(4-amino-1-piperidinyl)acetate		C₁₁H₂₂N₂O₂	详情	详情
(VIII)	29299	4-Amino-5-chloro-2-methoxybenzoic acid methoxycarbonyl anhydride		C₁₀H₁₀ClNO₅	详情	详情

Extended Information