2-hydroxy-2-phenylacetic acid -Drug Synthesis Database

【结构式】

【分子编号】28161

【品名】2-hydroxy-2-phenylacetic acid

【CA登记号】611-72-3

【分子式】C₈H₈O₃

【分子量】152.14972

【元素组成】C 63.15% H 5.3% O 31.55%

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：(III)

This compound has been obtained by two related ways: 1) The reaction of the potassium salt of the nicotinic acid with oxalyl chloride in benzene gives the corresponding anhydride (II), which is condensed with 2-hydroxy-2-phenylacetic acid (III) in dioxane to yield the expected ester (IV). The reaction of (IV) with SOCl2 in dichloromethane affords 2-(nicotinoyloxy)-2-phenylacetyl chloride (V), which is finally esterified with the cyclohexanol (VI) in dichloromethane. 2) By acylation of the 2-hydroxy-2-phenylacetic acid cis-3,3,5-trimethylcyclohexyl ester (VII) with nicotinoyl chloride (VIII) in pyridine.

参考文献中间体

合成目标

【1】 Verga, A. (Ravizza SpA); New process for preparing cis-3,3,5-trimethylcyclohexyl-D,L-alpha-(3-pyridinecarboxy)-phenylacetate. EP 0157151 .
【2】 Mauri, F. (Gaver SA); Novel spasmolytic cpd. and process for its preparation. BE 0824034; DE 2461909; FR 2256757; JP 1975105670 .

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)	10752	Nicotinic acid; Niacin	59-67-6	C₆H₅NO₂	详情	详情
(II)	35737	nicotinic anhydride	16837-38-0	C₁₂H₈N₂O₃	详情	详情
(III)	28161	2-hydroxy-2-phenylacetic acid	611-72-3	C₈H₈O₃	详情	详情
(IV)	35738	2-phenyl-2-[(3-pyridinylcarbonyl)oxy]acetic acid		C₁₄H₁₁NO₄	详情	详情
(V)	35739	2-chloro-2-oxo-1-phenylethyl nicotinate		C₁₄H₁₀ClNO₃	详情	详情
(VI)	35740	(1R,5R)-3,3,5-trimethylcyclohexanol		C₉H₁₈O	详情	详情
(VII)	35741	(1R,5R)-3,3,5-trimethylcyclohexyl 2-hydroxy-2-phenylacetate	456-59-7	C₁₇H₂₄O₃	详情	详情
(VIII)	10753	Nicotinoyl chloride		C₆H₄ClNO	详情	详情

合成路线2

该中间体在本合成路线中的序号：(B)

AHR-53338 is synthesized in an overall yield of 62% from ethyl isonipecotate (I): Ethyl isonipecotate (I) is protected with benzyl bromide (II) to give (III), which is then treated with 2.5 moles of 4-fluorophenylmagnesium bromide to give the tertiary alcohol (IV). The benzyl group is removed by catalytic hydrogenolysis to give the secondary piperidine (V). The reaction of 1-bromo-3-chloropropane (VI) with acetovanillone (VII) gives 1-[4-(3-chloropropoxy)-3-methoxyphenyl]ethanone (VIII) in excellent yield. A mixture of (V) and (VIII) in 1-butanol and triethylamine heated at reflux yields AHR-53338 isolated as the mandelic acid salt.

参考文献中间体

合成目标

【1】 Yanni, J.M.; Walsh, D.A.; Franzyshen, S.K.; The synthesis and antiallergy activity of 1-[4-[3-. 193rd ACS Natl Meet 1987, Abst MEDI 85.
【2】 Yanni, J.M.; Walsh, D.A.; AHR-5333B. Drugs Fut 1988, 13, 7, 605.

中间体序号	中间体编号	品名	CAS号	分子式	供应商	用于合成
(A)	13643	4-fluorophenyl magnesium bromide;Bromo(4-fluorophenyl)magnesium;bromo(p-fluorophenyl)Magnesium;p-Fluorophenylmagnesium bromide	352-13-6	C₆H₄BrFMg	详情	详情
(B)	28161	2-hydroxy-2-phenylacetic acid	611-72-3	C₈H₈O₃	详情	详情
(I)	17410	Ethyl isonipecotate; ethyl 4-piperidinecarboxylate	1126-09-6	C₈H₁₅NO₂	详情	详情
(II)	12912	1-(Bromomethyl)benzene; Alpha-bromotoluene	100-39-0	C₇H₇Br	详情	详情
(III)	22600	ethyl 1-benzyl-4-piperidinecarboxylate; N-Benzyl-4-carbethoxy piperidine	24228-40-8	C₁₅H₂₁NO₂	详情	详情
(IV)	22601	(1-benzyl-4-piperidinyl)[bis(4-fluorophenyl)]methanol		C₂₅H₂₅F₂NO	详情	详情
(V)	22602	bis(4-fluorophenyl)(4-piperidinyl)methanol	60284-98-2	C₁₈H₁₉F₂NO	详情	详情
(VI)	10358	1-Bromo-3-chloropropane	109-70-6	C₃H₆BrCl	详情	详情
(VII)	22604	1-(4-hydroxy-3-methoxyphenyl)-1-ethanone；Acetovanillone;4’-hydroxy-3’-methoxyacetophenone;1-(4-hydroxy-3-methoxyphenyl)ethanone	498-02-2	C₉H₁₀O₃	详情	详情
(VIII)	22605	4-(3-Chloropropoxy)-3-Methoxyacetophenone;3-(4-Acetyl-2-methoxyphenoxy)propyl chloride;1-(4-(3-chloropropoxy)-3-methoxyphenyl)ethanone;1-[4-(3-chloropropoxy)-3-methoxyphenyl]-1-ethanone	58113-30-7	C₁₂H₁₅ClO₃	详情	详情

Extended Information