2-[(2R)-2-(3,4-difluorophenyl)morpholinyl]ethyl benzoate -Drug Synthesis Database

【结构式】

【分子编号】54989

【品名】2-[(2R)-2-(3,4-difluorophenyl)morpholinyl]ethyl benzoate

【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：(X)

Cyanohydrin (II) was prepared by addition of KCN to 3,4-difluorobenzaldehyde (I) in the presence of sodium bisulfite. After protection of the hydroxyl group of (II) as the tetrahydropyranyl ether (III), alkylation with bromoethyl benzoate (IV) in the presence of LDA furnished adduct (V). Catalytic hydrogenation of the cyano group to give (VI), followed by tetrahydropyranyl group cleavage under acidic conditions, afforded amino alcohol (VII). Subsequent acylation of (VII) with chloroacetyl chloride produced the chloroacetamide (VIII). Intramolecular cyclization of (VIII) upon treatment with K2CO3 in boiling toluene yielded a racemic morpholinone that was resolved into the enantiomers by using L-tartaric acid. The desired (R)-morpholinone (IX) was then reduced to the corresponding morpholine (X) employing borane in THF.

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
(I)	26654	3,4-difluorobenzaldehyde	34036-07-2	C₇H₄F₂O	详情	详情
(II)	54981	2-(3,4-difluorophenyl)-2-hydroxyacetonitrile		C₈H₅F₂NO	详情	详情
(III)	54982	2-(3,4-difluorophenyl)-2-(tetrahydro-2H-pyran-2-yloxy)acetonitrile		C₁₃H₁₃F₂NO₂	详情	详情
(IV)	54983	2-Bromoethyl benzoate; Benzoic acid 2-bromoethyl ester	939-54-8	C₉H₉BrO₂	详情	详情
(V)	54984	3-cyano-3-(3,4-difluorophenyl)-3-(tetrahydro-2H-pyran-2-yloxy)propyl benzoate		C₂₂H₂₁F₂NO₄	详情	详情
(VI)	54985	4-amino-3-(3,4-difluorophenyl)-3-(tetrahydro-2H-pyran-2-yloxy)butyl benzoate		C₂₂H₂₅F₂NO₄	详情	详情
(VII)	54986	4-amino-3-(3,4-difluorophenyl)-3-hydroxybutyl benzoate		C₁₇H₁₇F₂NO₃	详情	详情
(VIII)	54987	4-[(2-chloroacetyl)amino]-3-(3,4-difluorophenyl)-3-hydroxybutyl benzoate		C₁₉H₁₈ClF₂NO₄	详情	详情
(IX)	54988	2-[(2R)-2-(3,4-difluorophenyl)-5-oxomorpholinyl]ethyl benzoate		C₁₉H₁₇F₂NO₄	详情	详情
(X)	54989	2-[(2R)-2-(3,4-difluorophenyl)morpholinyl]ethyl benzoate		C₁₉H₁₉F₂NO₃	详情	详情

合成路线2

该中间体在本合成路线中的序号：(X)

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

Extended Information