tert-butyl 2-[(allyloxy)imino]-3-(3,4-dichlorophenyl)-5-oxopentyl(methyl)carbamate -Drug Synthesis Database

【结构式】

【分子编号】60820

【品名】tert-butyl 2-[(allyloxy)imino]-3-(3,4-dichlorophenyl)-5-oxopentyl(methyl)carbamate

【CA登记号】

【分子式】C₂₀H₂₆Cl₂N₂O₄

【分子量】429.34292

【元素组成】C 55.95% H 6.1% Cl 16.51% N 6.52% O 14.91%

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：(XIV)

Claisen condensation between 3,4-dichlorophenylacetic acid (VI) and N-Boc-sarcosine methyl ester (VII), followed by acidic decarboxylation of the intermediate keto acid, furnishes amino ketone (VIII). Alkylation of (VIII) with the silylated bromoethanol (IX) in the presence of NaH and NaI yields adduct (X). Subsequent condensation of ketone (X) with O-allyl hydroxylamine (XI) generates the corresponding oxime (XII). After desilylation of (XII) with tetrabutylammonium fluoride, the resultant primary alcohol (XIII) is oxidized under Swern conditions to furnish aldehyde (XIV)

参考文献中间体

合成目标

【1】 Carruthers, N.I.; Alaimo, C.A.; Shih, N.-Y.; Lavey, B.J.; Ting, P.C.; Reichard, G.A. (Schering Corp.); Substd. oximes as neurokinin antagonists. EP 1032561; WO 9926924 .
【2】 Carruthers, N.I.; Reichard, G.A.; Shih, N.-Y.; Lavey, B.J.; Alaimo, C.A.; Ting, P.C. (Schering Corp.); Substd. oximes as neurokinin antagonists. US 6063926 .

中间体序号	中间体编号	品名	CAS号	分子式	供应商	用于合成
(VI)	30414	2-(3,4-dichlorophenyl)acetic acid；2-(3,4-Dichlorophenyl)acetic acid	5807-30-7	C₈H₆Cl₂O₂	详情	详情
(VII)	60815	methyl 2-[(tert-butoxycarbonyl)(methyl)amino]acetate		C₉H₁₇NO₄	详情	详情
(VIII)	60816	tert-butyl 3-(3,4-dichlorophenyl)-2-oxopropyl(methyl)carbamate		C₁₅H₁₉Cl₂NO₃	详情	详情
(IX)	55573	2-Bromoethoxy-t-butyldimethylsilane	86864-60-0	C₈H₁₉BrOSi	详情	详情
(X)	60817	tert-butyl 5-{[tert-butyl(dimethyl)silyl]oxy}-3-(3,4-dichlorophenyl)-2-oxopentyl(methyl)carbamate		C₂₃H₃₇Cl₂NO₄Si	详情	详情
(XI)	49195	3-(aminooxy)-1-propene; O-allylhydroxylamine		C₃H₇NO	详情	详情
(XII)	60818	tert-butyl 2-[(allyloxy)imino]-5-{[tert-butyl(dimethyl)silyl]oxy}-3-(3,4-dichlorophenyl)pentyl(methyl)carbamate		C₂₆H₄₂Cl₂N₂O₄Si	详情	详情
(XIII)	60819	tert-butyl 2-[(allyloxy)imino]-3-(3,4-dichlorophenyl)-5-hydroxypentyl(methyl)carbamate		C₂₀H₂₈Cl₂N₂O₄	详情	详情
(XIV)	60820	tert-butyl 2-[(allyloxy)imino]-3-(3,4-dichlorophenyl)-5-oxopentyl(methyl)carbamate		C₂₀H₂₆Cl₂N₂O₄	详情	详情

合成路线2

该中间体在本合成路线中的序号：(XIV)

Reductive condensation between aldehyde (XIV) and the piperidine derivative (V) in the presence of NaBH3CN leads to the N-alkylated piperidine (XV). The N-Boc group of (XV) is cleaved under acidic conditions to afford amine (XVI), which is further acylated by 3,5-dichlorobenzoyl chloride (XVII), providing benzamide (XVIII). The oxime O-allyl group of (XVIII) is then removed by treatment with palladium tetrakis(triphenylphosphine) and triethylammonium formate, yielding oxime (XIX). This is subsequently alkylated with bromoacetonitrile and NaH, affording (XX)

参考文献中间体

合成目标

【1】 Carruthers, N.I.; Alaimo, C.A.; Shih, N.-Y.; Lavey, B.J.; Ting, P.C.; Reichard, G.A. (Schering Corp.); Substd. oximes as neurokinin antagonists. EP 1032561; WO 9926924 .
【2】 Carruthers, N.I.; Reichard, G.A.; Shih, N.-Y.; Lavey, B.J.; Alaimo, C.A.; Ting, P.C. (Schering Corp.); Substd. oximes as neurokinin antagonists. US 6063926 .

中间体序号	中间体编号	品名	CAS号	分子式	供应商	用于合成
(V)	44280	N-(4-Piperidine)-2-piperidinone		C₁₀H₁₈N₂O	详情	详情
(XIV)	60820	tert-butyl 2-[(allyloxy)imino]-3-(3,4-dichlorophenyl)-5-oxopentyl(methyl)carbamate		C₂₀H₂₆Cl₂N₂O₄	详情	详情
(XV)	60821			C₃₀H₄₄Cl₂N₄O₄	详情	详情
(XVI)	60822			C₂₅H₃₆Cl₂N₄O₂	详情	详情
(XVII)	27769	3,5-dichlorobenzoyl chloride	2905-62-6	C₇H₃Cl₃O	详情	详情
(XVIII)	60823			C₃₂H₃₈Cl₄N₄O₃	详情	详情
(XIX)	60824			C₂₉H₃₄Cl₄N₄O₃	详情	详情
(XX)	60825			C₃₁H₃₅Cl₄N₅O₃	详情	详情

Extended Information