ethyl (3S)-3-piperidinecarboxylate -Drug Synthesis Database

【结构式】

【分子编号】35224

【品名】ethyl (3S)-3-piperidinecarboxylate

【CA登记号】

【分子式】C₈H₁₅NO₂

【分子量】157.21264

【元素组成】C 61.12% H 9.62% N 8.91% O 20.35%

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：(V)

Addition of cyclopropylmagnesium bromide (II) to dibenzocycloheptanone (I) afforded the carbinol adduct (III), which was further rearranged to the bromopropylidene derivative (IV) upon treatment with bromotrimethylsilane. Alkylation of ethyl (R)-nipecotate (V) with bromide (IV) gave the tertiary amine (VI). The ethyl ester group of (VI) was finally hydrolyzed under basic conditions to furnish the corresponding carboxylic acid.

参考文献中间体

合成目标

【1】 Andersen, K.E.; Olsen, U.B.; Petersen, H.; Grønvald, F.C.; Sonnewald, U.; Jørgensen, T.K.; Andersen, H.S. (Novo Nordisk A/S); Novel heterocyclic cpds.. US 5595989; US 5668129; US 5688788; US 5693649; US 5712292; US 5721254; US 5795888; US 6043239; WO 9518793 .
【2】 Olsen, U.B. (Novo Nordisk A/S); Novel method. JP 1999507947; WO 9722338 .

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)	40123	10,11-dihydro-5H-dibenzo[a,d]cyclohepten-5-one; Dibenzosuberone	1210-35-1	C₁₅H₁₂O	详情	详情
(II)	12450	Bromo(cyclopropyl)magnesium;cyclopropylmagnesium bromide;cyclopropylmagnesiumbromide	23719-80-4	C₃H₅BrMg	详情	详情
(III)	52138	5-cyclopropyl-10,11-dihydro-5H-dibenzo[a,d]cyclohepten-5-ol		C₁₈H₁₈O	详情	详情
(IV)	52139	5-(3-bromopropylidene)-10,11-dihydro-5H-dibenzo[a,d]cycloheptene		C₁₈H₁₇Br	详情	详情
(V)	35224	ethyl (3S)-3-piperidinecarboxylate		C₈H₁₅NO₂	详情	详情
(VI)	52140	ethyl (3R)-1-[3-(10,11-dihydro-5H-dibenzo[a,d]cyclohepten-5-ylidene)propyl]-3-piperidinecarboxylate		C₂₆H₃₁NO₂	详情	详情

合成路线2

该中间体在本合成路线中的序号：(Ia),(II)

Racemic ethyl 3-piperidinecarboxylate (Ia, Ib) was resolved with D-(-)-tartaric acid in EtOH to afford the (S)-piperidine tartrate salt (II). After protection of (II) as the N-Boc derivative (III) by treatment with di-tert-butyl dicarbonate and NaOH, reduction of the carboxylate group of (III) by means of LiBH4 provided alcohol (IV). Subsequent coupling of (IV) with 4-bromo-2,6-dimethylphenol (V) under Mitsunobu conditions provided ether (VI). The N-Boc protecting group of (VI) was then cleaved employing trifluoroacetic acid to give piperidine (VII). Finally, Eschweiler-Clarke methylation using formaldehyde and formic acid furnished the corresponding N-methyl piperidine, which was isolated after conversion to the hydrochloride salt.

参考文献中间体

合成目标

【1】 Kojima, N.; Nishino, C. (Shiseido Co. Ltd.); Benzamide deriv., anti-ulcer drug, and antibacterial drug. EP 0869124; JP 1998279570; US 5891890 .

中间体序号	中间体编号	品名	CAS号	分子式	供应商	用于合成
(Ib)	12453	ethyl (3R)hexahydro-3-pyridinecarboxylate		C₈H₁₅NO₂	详情	详情
(Ia),(II)	35224	ethyl (3S)-3-piperidinecarboxylate		C₈H₁₅NO₂	详情	详情
(III)	35220	1-(tert-butyl) 3-ethyl (3S)-1,3-piperidinedicarboxylate		C₁₃H₂₃NO₄	详情	详情
(IV)	35221	tert-butyl (3S)-3-(hydroxymethyl)-1-piperidinecarboxylate		C₁₁H₂₁NO₃	详情	详情
(V)	31142	4-bromo-2,6-dimethylphenol	2374-05-2	C₈H₉BrO	详情	详情
(VI)	35222	tert-butyl (3S)-3-[(4-bromo-2,6-dimethylphenoxy)methyl]-1-piperidinecarboxylate		C₁₉H₂₈BrNO₃	详情	详情
(VII)	35223	(3S)-3-[(4-bromo-2,6-dimethylphenoxy)methyl]piperidine; 4-bromo-2,6-dimethylphenyl (3S)piperidinylmethyl ether		C₁₄H₂₀BrNO	详情	详情

Extended Information