5-(hydroxymethyl)-2-nitrophenol -Drug Synthesis Database

【结构式】

【分子编号】21465

【品名】5-(hydroxymethyl)-2-nitrophenol

【CA登记号】

【分子式】C₇H₇NO₄

【分子量】169.13692

【元素组成】C 49.71% H 4.17% N 8.28% O 37.84%

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：(II)

A synthesis of the racemic compound was later reported: 3-Hydroxy-4-nitrobenzaldehyde (I) was reduced to the benzyl alcohol (II) with NaBH4 and then converted to diacetate (III) with Ac2O in pyridine. Selective deacetylation of the aryl ester of (III) with KHCO3 in MeOH produced phenol (IV), which was then acylated with acetylsalicyloyl chloride (V) to yield (VI). The catalytic hydrogenation of the nitro group of (VI) in the presence of Raney-Ni was accompanied by migration of the salicyloyl unit to the amino group to yield salicylamide (VII) (accompanied by some byproduct resulting from the cleavage of the phenolic acetate). The resultant mixture of mono- and diacetate was converted to triol (VIII) by hydrolysis in aqueous NaOH. Then, the aminophenol ring of (VIII) was selectively oxidized with Fremy's salt to quinone (IX). Finally, the quinone was treated with H2O2 in the presence of NaHCO3 to furnish the racemic epoxide.

参考文献中间体

合成目标

【1】 Matsumoto, N.; Iinuma, H.; Sawa, T.; Takeuchi, T.; Synthesis of anti-rheumatic agent epoxyquinomicin B. Bioorg Med Chem Lett 1998, 8, 21, 2945.
【2】 Matsumoto, N.; et al.; Epoxyquinomicins A, B, C and D, new antibiotics from Amycolatopsis. I. Taxonomy, fermentation, isolation and antimicrobial activities. J Antibiot 1997, 50, 11, 900.

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)	21032	3-hydroxy-4-nitrobenzaldehyde		C₇H₅NO₄	详情	详情
(II)	21465	5-(hydroxymethyl)-2-nitrophenol		C₇H₇NO₄	详情	详情
(III)	21466	5-[(acetoxy)methyl]-2-nitrophenyl acetate		C₁₁H₁₁NO₆	详情	详情
(IV)	21467	3-hydroxy-4-nitrobenzyl acetate		C₉H₉NO₅	详情	详情
(V)	16900	2-(chlorocarbonyl)phenyl acetate; Acetylsalicyloyl chloride	5538-51-2	C₉H₇ClO₃	详情	详情
(VI)	21469	5-[(acetoxy)methyl]-2-nitrophenyl 2-(acetoxy)benzoate		C₁₈H₁₅NO₈	详情	详情
(VII)	21470	4-[[2-(acetoxy)benzoyl]amino]-3-hydroxybenzyl acetate		C₁₈H₁₇NO₆	详情	详情
(VIII)	21471	2-hydroxy-N-[2-hydroxy-4-(hydroxymethyl)phenyl]benzamide		C₁₄H₁₃NO₄	详情	详情
(IX)	21472	2-hydroxy-N-[4-(hydroxymethyl)-3,6-dioxo-1,4-cyclohexadien-1-yl]benzamide		C₁₄H₁₁NO₅	详情	详情

合成路线2

该中间体在本合成路线中的序号：(XVI)

Synthesis of intermediates (XX) and (XXIII): Coupling of methyl L-lactate (XII) with morpholine in presence of NaH yields amide (XIII) which is tosylated by means of NaH and p-TsCl in THF to afford (XIV). Reduction of carboxylic acid (XV) in DCE with B(OCH3)3, boron trifluoride diethyl etherate and BH3·pyr complex provides alcohol (XVI) which is then condensed with (XIV) in presence of K2CO3 in DMF to yield (XVII). Mesylation of (XVII) with MsCl in presence of Et3N in CH2Cl2 affords (XVIII), which reacts with potassium phthalimide (C) in DMF to give (XIX). Hydrogenation of phthalimide (XIX) with H2 over Pd/C in DMF provides derivative (XX). The treatment of (XIX) with NH2NH2 and p-TsOH gives amine (XXI), which is protected with di-t-butyl-dicarbonate to yield (XXII). Finally (XXIII) is obtained by reduction of the nitro moiety of (XXII) with H2 over Pd/C in EtOAc.

参考文献中间体

合成目标

【1】 Katayama, S.; Kishimoto, H.; Ae, N.; Nagata, R. (Sumitomo Pharmaceuticals Co., Ltd.); Tricyclic indole-2-carboxylic acid cpd. used as NMDA receptor antagonist. WO 0056711 .

中间体序号	中间体编号	品名	CAS号	分子式	供应商	用于合成
(XII)	17075	propionic acid, 2-hydroxy-, methyl ester, (S)-; methyl (2S)-2-hydroxypropanoate	27871-49-4	C₄H₈O₃	详情	详情
(XIII)	41498	(2S)-2-hydroxy-1-(4-morpholinyl)-1-propanone		C₇H₁₃NO₃	详情	详情
(XIV)	41499	(1S)-1-methyl-2-(4-morpholinyl)-2-oxoethyl 4-methylbenzenesulfonate		C₁₄H₁₉NO₅S	详情	详情
(XV)	41500	3-hydroxy-4-nitrobenzoic acid	619-14-7	C₇H₅NO₅	详情	详情
(XVI)	21465	5-(hydroxymethyl)-2-nitrophenol		C₇H₇NO₄	详情	详情
(XVII)	41501	(2R)-2-[5-(hydroxymethyl)-2-nitrophenoxy]-1-(4-morpholinyl)-1-propanone		C₁₄H₁₈N₂O₆	详情	详情
(XVIII)	41502	(2R)-2-[5-([[methyl(dimethylene)-lambda(6)-sulfanyl]oxy]methyl)-2-nitrophenoxy]-1-(4-morpholinyl)-1-propanone		C₁₇H₂₄N₂O₆S	详情	详情
(XIX)	41503	2-(3-[[(1R)-1-methyl-2-(4-morpholinyl)-2-oxoethyl]oxy]-4-nitrobenzyl)-1H-isoindole-1,3(2H)-dione		C₂₂H₂₁N₃O₇	详情	详情
(XX)	41506	2-(4-amino-3-[[(1R)-1-methyl-2-(4-morpholinyl)-2-oxoethyl]oxy]benzyl)-1H-isoindole-1,3(2H)-dione		C₂₂H₂₃N₃O₅	详情	详情
(XXI)	41504	(2R)-2-[5-(aminomethyl)-2-nitrophenoxy]-1-(4-morpholinyl)-1-propanone		C₁₄H₁₉N₃O₅	详情	详情
(XXII)	41505	tert-butyl 3-[[(1R)-1-methyl-2-(4-morpholinyl)-2-oxoethyl]oxy]-4-nitrobenzylcarbamate		C₁₉H₂₇N₃O₇	详情	详情
(XXIII)	41507	tert-butyl 4-amino-3-[[(1R)-1-methyl-2-(4-morpholinyl)-2-oxoethyl]oxy]benzylcarbamate		C₁₉H₂₉N₃O₅	详情	详情
(C)	27890	Potassium phthalimide	1074-82-4	C₈H₄KNO₂	详情	详情

Extended Information