[(2R)-2-(3,4-difluorophenyl)-2-(2-hydroxyethyl)morpholinyl](phenyl)methanone -Drug Synthesis Database

【结构式】

【分子编号】54991

【品名】[(2R)-2-(3,4-difluorophenyl)-2-(2-hydroxyethyl)morpholinyl](phenyl)methanone

【CA登记号】

【分子式】C₁₉H₁₉F₂NO₃

【分子量】347.3616064

【元素组成】C 65.7% H 5.51% F 10.94% N 4.03% O 13.82%

与该中间体有关的原料药合成路线共 2 条

合成路线1 合成路线2

合成路线1

该中间体在本合成路线中的序号：(XIII)

Benzamide (XII) was prepared by acylation of morpholine (X) with benzoyl chloride (XI). The benzoate ester of (XII) was subsequently hydrolyzed under basic conditions to the alcohol (XIII), which was further converted to the mesylate ester (XIV) by means of methanesulfonyl chloride and triethylamine.

参考文献中间体

合成目标

【1】 Emonds-Alt, X.; Grossriether, I.; Gueule, P.; Proietto, V.; Van Broeck, D. (Sanofi-Synthélabo); Substd. heterocyclic cpds., preparation method therefor and pharmaceutical compsns. containing same. EP 1156049; FR 2729952; FR 2729953; FR 2729954; JP 1999507324; JP 2001131171; US 5641777; WO 9623787 .

中间体序号	中间体编号	品名	CAS号	分子式	供应商	用于合成
(X)	54989	2-[(2R)-2-(3,4-difluorophenyl)morpholinyl]ethyl benzoate		C₁₉H₁₉F₂NO₃	详情	详情
(XI)	10463	Benzoyl chloride	98-88-4	C₇H₅ClO	详情	详情
(XII)	54990	2-[(2R)-4-benzoyl-2-(3,4-difluorophenyl)morpholinyl]ethyl benzoate		C₂₆H₂₃F₂NO₄	详情	详情
(XIII)	54991	[(2R)-2-(3,4-difluorophenyl)-2-(2-hydroxyethyl)morpholinyl](phenyl)methanone		C₁₉H₁₉F₂NO₃	详情	详情
(XIV)	54992	2-[(2R)-4-benzoyl-2-(3,4-difluorophenyl)morpholinyl]ethyl methanesulfonate		C₂₀H₂₁F₂NO₅S	详情	详情

合成路线2

该中间体在本合成路线中的序号：(XIII)

In an alternative process, the chiral morpholino alcohol (XIII) was activated as the sulfonate ester (XX) employing benzenesulfonyl chloride under phase-transfer conditions. Condensation of the alkyl sulfonate (XX) with 4-(tert-butoxycarbonylamino)-4-phenylpiperidine (XXI) afforded the N-substituted piperidine (XXII). The Boc protecting group of (XXII) was then removed by means of a methanolic solution of HCl, yielding the primary amine (XXIII). Alternatively, amine (XXIII) was synthesized by condensation of sulfonate (XX) with 4-amino-4-phenylpiperidine (XXIV) (obtained by catalytic hydrogenolysis of the N-benzyl piperidine (XVII)). Aminopiperidine (XXIII) was finally converted to the title urea by reaction with phosgene, followed by condensation with dimethylamine.

参考文献中间体

合成目标

【1】 Bonnefoy, S.; Aulombard, A.; Lucas, E.; Bernon, F.; Burgos, A.; Cabos, C. (Sanofi-Synthélabo); Method for preparing (R)-(+)-3-[1-[2-(4-benzoyl-2-(2,3-difluorophenyl)morpholin-2-yl)ethyl]-4-phenylpiperidin-4-yl]-1,1-dimethylurea, its salts solvates and/or hydrates. FR 2787790; US 6392039; WO 0039126 .

中间体序号	中间体编号	品名	分子式	供应商	用于合成
(XIII)	54991	[(2R)-2-(3,4-difluorophenyl)-2-(2-hydroxyethyl)morpholinyl](phenyl)methanone	C₁₉H₁₉F₂NO₃	详情	详情
(XVII)	54994	1-benzyl-4-phenyl-4-piperidinylamine; 1-benzyl-4-phenyl-4-piperidinamine	C₁₈H₂₂N₂	详情	详情
(XX)	54997	2-[(2R)-4-benzoyl-2-(3,4-difluorophenyl)morpholinyl]ethyl benzenesulfonate	C₂₅H₂₃F₂NO₅S	详情	详情
(XXI)	54998	tert-butyl 4-phenyl-4-piperidinylcarbamate	C₁₆H₂₄N₂O₂	详情	详情
(XXII)	54999	tert-butyl 1-{2-[(2R)-4-benzoyl-2-(3,4-difluorophenyl)morpholinyl]ethyl}-4-phenyl-4-piperidinylcarbamate	C₃₅H₄₁F₂N₃O₄	详情	详情
(XXIII)	55000	[(2R)-2-[2-(4-amino-4-phenyl-1-piperidinyl)ethyl]-2-(3,4-difluorophenyl)morpholinyl](phenyl)methanone	C₃₀H₃₃F₂N₃O₂	详情	详情
(XXIV)	55001	4-phenyl-4-piperidinylamine; 4-phenyl-4-piperidinamine	C₁₁H₁₆N₂	详情	详情

Extended Information