3-hydroxyacetophenone; 1-(3-hydroxyphenyl)-1-ethanone -Drug Synthesis Database

【结构式】

【分子编号】25331

【品名】3-hydroxyacetophenone; 1-(3-hydroxyphenyl)-1-ethanone

【CA登记号】121-71-1

【分子式】C₈H₈O₂

【分子量】136.15032

【元素组成】C 70.57% H 5.92% O 23.5%

与该中间体有关的原料药合成路线共 6 条

合成路线1 合成路线2 合成路线3 合成路线4 合成路线5 合成路线6

合成路线1

该中间体在本合成路线中的序号：(I)

3'-Hydroxyacetophenone (I) is acylated with pivaloylchloride (II) to form 3'-pivaloyloxyacetophenone (III). The latter is brominated with bromine to 3'-pivaloyloxy-2-bromoacetophenone (IV), which in turn reacts with N-ethylbenzylamine (V) to form 3'-pivaloyloxy-2-(benzylethylamino)acetophenone (VI). This compound is debenzylated and reduced with H2 in the presence of Pd/C in isopropanol containing hydrochloric acid to yield etilefrine pivalate hydrochloride.

参考文献中间体

合成目标

【1】 St Janiak, P.; Etilefrine Pivalate. Drugs Fut 1979, 4, 6, 413.

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)	25331	3-hydroxyacetophenone; 1-(3-hydroxyphenyl)-1-ethanone	121-71-1	C₈H₈O₂	详情	详情
(II)	13597	2,2-Dimethylpropanoyl chloride; Pivaloyl chloride	3282-30-2	C₅H₉ClO	详情	详情
(III)	39466	3-acetylphenyl pivalate		C₁₃H₁₆O₃	详情	详情
(IV)	39467	3-(2-bromoacetyl)phenyl pivalate		C₁₃H₁₅BrO₃	详情	详情
(V)	39468	N-benzyl-N-ethylamine; N-benzyl-1-ethanamine	14321-27-8	C₉H₁₃N	详情	详情
(VI)	39469	3-[2-[benzyl(ethyl)amino]acetyl]phenyl pivalate		C₂₂H₂₇NO₃	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 intermediate alcohol (VIII) was prepared as shown in Scheme 27060901a: Aldol condensation of 3,4-dimethoxybenzaldehyde (I) with 3-hydroxyacetophenone (II) in the presence of KOH provided chalcone (III), which was hydrogenated over Pd/C to yield the corresponding diarylpropanone (IV). Subsequent alkylation of the phenolic hydroxyl group of (IV) with tert-butyl bromoacetate (V) using NaH in DMF gave ether (VI). Then, enantioselective reduction of ketone by means of (+)-beta-chlorodiisopinocampheylborane (VII) at -20 C furnished the (R)-alcohol (VIII).

参考文献中间体

合成目标

【1】 Yang, W.; Guo, T.; Keenan, T.P.; Laborde, E.; Holt, D.A. (Ariad Pharmaceuticals Inc.); Synthetic derivs. of rapamycin as multimerizing agents for chimeric proteins with immunophilin-derived domains. JP 2000505475; WO 9731898 .

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)	18304	3,4-Dimethoxybenzaldehyde; Veratraldehyde	120-14-9	C₉H₁₀O₃	详情	详情
(II)	25331	3-hydroxyacetophenone; 1-(3-hydroxyphenyl)-1-ethanone	121-71-1	C₈H₈O₂	详情	详情
(III)	25332	(E)-3-(3,4-dimethoxyphenyl)-1-(3-hydroxyphenyl)-2-propen-1-one		C₁₇H₁₆O₄	详情	详情
(IV)	25341	3-(3,4-dimethoxyphenyl)-1-(3-hydroxyphenyl)-1-propanone		C₁₇H₁₈O₄	详情	详情
(V)	17430	2-Bromoacetic acid tert-butyl ester; tert-butyl 2-bromoacetate; tert-Butyl bromoacetate	5292-43-3	C₆H₁₁BrO₂	详情	详情
(VI)	25342	tert-butyl 2-[3-[3-(3,4-dimethoxyphenyl)propanoyl]phenoxy]acetate		C₂₃H₂₈O₆	详情	详情
(VII)	25343	chloro[bis[(1S,2R,3S,5S)-2,6,6-trimethylbicyclo[3.1.1]hept-3-yl]]borane	112246-73-8	C₂₀H₃₄BCl	详情	详情
(VIII)	25348	tert-butyl 2-[3-[(1R)-3-(3,4-dimethoxyphenyl)-1-hydroxypropyl]phenoxy]acetate		C₂₃H₃₀O₆	详情	详情

合成路线3

该中间体在本合成路线中的序号：(I)

Selective protection of the 7-hydroxyl group of deacetylbaccatin (I) with triethylsilyl chloride provided silyl ether (II), which was acetylated at position 10 using acetyl chloride and lithium hexamethyldisilazide. Further coupling of (II) with beta-lactam (III) gave (IV), which by selective removal of the 7-silyl group with 0.1 N HCl gave 10-acetyl-2'-(triisopropylsilyl)docetaxel (V). This was condensed with benzoylcinnamic acid (VI) employing EDC and DMAP to afford ester (VII).

参考文献中间体

合成目标

【1】 Ahern, D.G.; Ojima, I.; Bounaud, P.-Y.; New photoaffinity analogs of paclitaxel. Bioorg Med Chem Lett 1999, 9, 8, 1189.

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)	25331	3-hydroxyacetophenone; 1-(3-hydroxyphenyl)-1-ethanone	121-71-1	C₈H₈O₂	详情	详情
(II)	25332	(E)-3-(3,4-dimethoxyphenyl)-1-(3-hydroxyphenyl)-2-propen-1-one		C₁₇H₁₆O₄	详情	详情
(III)	25333	tert-butyl (3R,4S)-2-oxo-4-phenyl-3-[(triisopropylsilyl)oxy]-1-azetidinecarboxylate		C₂₃H₃₇NO₄Si	详情	详情
(IV)	25334	(1S,2S,3R,4S,7R,9S,10S,12R,15S)-4,12-bis(acetoxy)-15-([(2R,3S)-3-[(tert-butoxycarbonyl)amino]-3-phenyl-2-[(triisopropylsilyl)oxy]propanoyl]oxy)-1-hydroxy-10,14,17,17-tetramethyl-11-oxo-9-[(triethylsilyl)oxy]-6-oxatetracyclo[11.3.1.0(3,10).0(4,7)]h		C₆₀H₈₉NO₁₅Si₂	详情	详情
(V)	25335	(1S,2S,3R,4S,7R,9S,10R,12R,15S)-4,12-bis(acetoxy)-15-([(2R,3S)-3-[(tert-butoxycarbonyl)amino]-3-phenyl-2-[(triisopropylsilyl)oxy]propanoyl]oxy)-1,9-dihydroxy-10,14,17,17-tetramethyl-11-oxo-6-oxatetracyclo[11.3.1.0(3,10).0(4,7)]heptadec-13-en-2-yl		C₅₄H₇₅NO₁₅Si	详情	详情
(VI)	25336	(E)-3-(3-benzoylphenyl)-2-propenoic acid		C₁₆H₁₂O₃	详情	详情
(VII)	25337	(1S,2S,3R,4S,7R,9S,10R,12R,15S)-4,12-bis(acetoxy)-9-[[(E)-3-(3-benzoylphenyl)-2-propenoyl]oxy]-15-([(2R,3S)-3-[(tert-butoxycarbonyl)amino]-3-phenyl-2-[(triisopropylsilyl)oxy]propanoyl]oxy)-1-hydroxy-10,14,17,17-tetramethyl-11-oxo-6-oxatetracyclo[1		C₇₀H₈₅NO₁₇Si	详情	详情

合成路线4

该中间体在本合成路线中的序号：(I)

Selective protection of the 7-hydroxyl group of deacetylbaccatin (I) with triethylsilyl chloride provided silyl ether (II), which was acylated at position 10 with the activated ester (III) in the presence of lithium hexamethyldisilazide to give the benzoylcinnamic ester (IV). Further coupling of (IV) with beta-lactam (V) gave (VI), which by removal of the silyl groups with HF in pyridine-acetonitrile afforded (VII). The Boc group of (VII) was then removed with trifluoroacetic acid to give amine (VIII).

参考文献中间体

合成目标

【1】 Ahern, D.G.; Ojima, I.; Bounaud, P.-Y.; New photoaffinity analogs of paclitaxel. Bioorg Med Chem Lett 1999, 9, 8, 1189.

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)	25331	3-hydroxyacetophenone; 1-(3-hydroxyphenyl)-1-ethanone	121-71-1	C₈H₈O₂	详情	详情
(II)	25341	3-(3,4-dimethoxyphenyl)-1-(3-hydroxyphenyl)-1-propanone		C₁₇H₁₈O₄	详情	详情
(III)	25344	2-[[(E)-3-(3-benzoylphenyl)-2-propenoyl]oxy]-1H-isoindole-1,3(2H)-dione		C₂₄H₁₅NO₅	详情	详情
(IV)	25345	(1S,2S,3R,4S,7R,9S,10S,12R,15S)-4-(acetoxy)-12-[[(E)-3-(3-benzoylphenyl)-2-propenoyl]oxy]-1,15-dihydroxy-10,14,17,17-tetramethyl-11-oxo-9-[(triethylsilyl)oxy]-6-oxatetracyclo[11.3.1.0(3,10).0(4,7)]heptadec-13-en-2-yl benzoate		C₅₁H₆₀O₁₂Si	详情	详情
(V)	25333	tert-butyl (3R,4S)-2-oxo-4-phenyl-3-[(triisopropylsilyl)oxy]-1-azetidinecarboxylate		C₂₃H₃₇NO₄Si	详情	详情
(VI)	25346	(1S,2S,3R,4S,7R,9S,10S,12R,15S)-4-(acetoxy)-12-[[(E)-3-(3-benzoylphenyl)-2-propenoyl]oxy]-15-([(2R,3S)-3-[(tert-butoxycarbonyl)amino]-3-phenyl-2-[(triisopropylsilyl)oxy]propanoyl]oxy)-1-hydroxy-10,14,17,17-tetramethyl-11-oxo-9-[(triethylsilyl)oxy]		C₇₄H₉₇NO₁₆Si₂	详情	详情
(VII)	25347	(1S,2S,3R,4S,7R,9S,10S,12R,15S)-4-(acetoxy)-12-[[(E)-3-(3-benzoylphenyl)-2-propenoyl]oxy]-15-([(2R,3S)-3-[(tert-butoxycarbonyl)amino]-2-hydroxy-3-phenylpropanoyl]oxy)-1,9-dihydroxy-10,14,17,17-tetramethyl-11-oxo-6-oxatetracyclo[11.3.1.0(3,10).0(4,		C₅₉H₆₃NO₁₆	详情	详情
(VIII)	25382	(1S,2S,3R,4S,7R,9S,10S,12R,15S)-4-(acetoxy)-15-[[(2R,3S)-3-amino-2-hydroxy-3-phenylpropanoyl]oxy]-12-[[(E)-3-(3-benzoylphenyl)-2-propenoyl]oxy]-1,9-dihydroxy-10,14,17,17-tetramethyl-11-oxo-6-oxatetracyclo[11.3.1.0(3,10).0(4,7)]heptadec-13-en-2-yl		C₅₄H₅₅NO₁₄	详情	详情

合成路线5

该中间体在本合成路线中的序号：(I)

参考文献中间体

合成目标

【1】 Jaweed M, Siddiqui M, Upadhye BK, et al. 2007. Process for preparing enantiomerically pure rivastigmine. W0 2007026373

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)	25331	3-hydroxyacetophenone; 1-(3-hydroxyphenyl)-1-ethanone	121-71-1	C₈H₈O₂	详情	详情
(II)	12964	3-[1-(Dimethylamino)ethyl]phenol		C₁₀H₁₅NO	详情	详情
(III)	12966	3-[1-(dimethylamino)ethyl]phenyl ethyl(methyl)carbamate		C₁₄H₂₂N₂O₂	详情	详情
(IV)	66627	2,3-bis((4-methylbenzoyl)oxy)succinic acid mixtures		C₂₀H₁₈O₈	详情	详情

合成路线6

该中间体在本合成路线中的序号：(I)

参考文献中间体

合成目标

【1】 Gaitonde A, Mangle M. 2005. Process for the preparation of aminoalkylphenyl carbamates in particular rivastigmine hydragentartrate. GB 2409453(本专利属于Generics UK Limited, UK)

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)	25331	3-hydroxyacetophenone; 1-(3-hydroxyphenyl)-1-ethanone	121-71-1	C₈H₈O₂	详情	详情
(II)	66637	2-(ethyl(methyl)amino)acetyl chloride		C₅H₁₀ClNO	详情	详情
(III)	66638	3-acetylphenyl ethyl(methyl)carbamate		C₁₂H₁₅NO₃	详情	详情
(IV)	66639	3-(1-(dimethylamino)ethyl)phenyl ethyl(methyl)carbamate hydrochloride		C₁₄H₂₂N₂O₂.HCl	详情	详情

Extended Information