methyl trifluoromethanesulfonate -Drug Synthesis Database

【结构式】

【分子编号】45233

【品名】methyl trifluoromethanesulfonate

【CA登记号】

【分子式】C₂H₃F₃O₃S

【分子量】164.1052296

【元素组成】C 14.64% H 1.84% F 34.73% O 29.25% S 19.54%

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：(IV)

The reduction of 11C-CO2 (I) by means of LiAlH4 in THF gives 11C-methanol (II), which is treated with 57 % IH to yield 11C-methyl iodide (III). The reaction of (III) with silver triflate affords 11C-methyl triflate (IV). Finally, (R)(-)-nor-selegiline (nor-deprenil) (V) is methylated with the radiolabeled methyl triflate (IV) by means of NaOH in aqueous acetone to obtain the target radiolabeled compound.

参考文献中间体

合成目标

【1】 Dolle, F.; et al.; Efficient synthesis and formulation of (R)-(-)-[11C]deprenyl, a selective radioligand for the quantification of MAO-B activity using PET. J Label Compd Radiopharm 2002, 45, 10, 803.

中间体序号	中间体编号	品名	CAS号	分子式	供应商	用于合成
(II)	58598	methanol		CH₄O	详情	详情
(III)	58599	iodomethane		CH₃I	详情	详情
(IV)	17414	methyl trifluoromethane sulfonate; methyl trifluoromethanesulfonate	333-27-7	C₂H₃F₃O₃S	详情	详情
(IV)	45233	methyl trifluoromethanesulfonate		C₂H₃F₃O₃S	详情	详情
(V)	58600	N-[(1R)-1-methyl-2-phenylethyl]-2-propyn-1-amine; N-[(1R)-1-methyl-2-phenylethyl]-N-(2-propynyl)amine		C₁₂H₁₅N	详情	详情

合成路线2

该中间体在本合成路线中的序号：(XXII)

3) Racemic MDL-100907 (VII) can also be obtained as follows: The reaction of piperidine-4-carboxylic acid ethyl ester (XVIII) with the previously mentioned bromide (II) by means of K2CO3 as before gives 1-[2-(4-fluorophenyl)ethyl]piperidine-4-carboxylic acid ethyl ester (XIX), which is treated with N,O-dimethylhydroxylamine (XIII) to afford carboxamide (XX). The condensation of (XX) with veratrole (VI) by means of BuLi as before yields the ketonic precursor (XVII), which is finally reduced as before. 4) [11C]-Radiolabeled MDL-100907 can be obtained as follows: Racemic MDL-100907 (VII) is treated with L-Selectride in THF, yielding racemic 1-[1-[2-(4-fluorophenyl)ethyl]piperidin-4-yl]-1-(3-hydroxy-2-methoxy-phenyl)methanol (rac-XXI), which is submitted to semi-preparative HPLC separation over Chiracel OD, affording pure (R-XXI). Finally, this compound is methylated with [11C]-methyl iodide and KOH in HMPA. If this methylation is performed with nonlabeled methyl iodide, MDL-100907 is obtained. 5) The radiolabeling of phenol (R-XXI) can also be performed with better yields using [11C]-methyl trifluoromethanesulfonate (XXII) as methylating agent. Triflate (XXII) is obtained by reaction of silver triflate with [11C]-methyl iodide.

参考文献中间体

合成目标

【1】 Mathis, C.A.; Mahmood, K.; Price, J.C.; Huang, Y.; Gerdes, J.M.; Simpson, N.R.; Synthesis and preliminary in vivo evaluation of [11C]MDL 100907: A potent and selective radioligand for the 5-HT2A receptor system. Med Chem Res 1996, 6, 1, 1-10.
【2】 Castaner, J.; Sorbera, L.A.; Silvestre, J.S.; MDL-100907. Drugs Fut 1998, 23, 9, 955.
【3】 Hiyama, T.; Minami, T.; Hanamoto, T.; Reddy, G.B. (Sagami Chemical Research Center); Optically active esters of 7-substd. 3,5-difunctionalized 6-heptenoic acids. EP 0475627 .

中间体序号	中间体编号	品名	CAS号	分子式	供应商	用于合成
(II)	17394	1-(2-bromoethyl)-4-fluorobenzene		C₈H₈BrF	详情	详情
(VI)	17398	2-methoxyphenyl methyl ether; Veratrole; 1,2-dimethoxybenzene	91-16-7	C₈H₁₀O₂	详情	详情
(VII)	17399	(2,3-dimethoxyphenyl)[1-(4-fluorophenethyl)-4-piperidinyl]methanol		C₂₂H₂₈FNO₃	详情	详情
(XIII)	13361	(Methoxyamino)methane; N,O-Dimethylhydroxylamine	1117-97-1	C₂H₇NO	详情	详情
(XVII)	17409	(2,3-dimethoxyphenyl)[1-(4-fluorophenethyl)-4-piperidinyl]methanone		C₂₂H₂₆FNO₃	详情	详情
(XVIII)	17410	Ethyl isonipecotate; ethyl 4-piperidinecarboxylate	1126-09-6	C₈H₁₅NO₂	详情	详情
(XIX)	17411	ethyl 1-(4-fluorophenethyl)-4-piperidinecarboxylate		C₁₆H₂₂FNO₂	详情	详情
(XX)	17412	1-(4-fluorophenethyl)-N-methoxy-N-methyl-4-piperidinecarboxamide		C₁₆H₂₃FN₂O₂	详情	详情
(XXI)	17413	3-[(R)-[1-(4-fluorophenethyl)-4-piperidinyl](hydroxy)methyl]-2-methoxyphenol		C₂₁H₂₆FNO₃	详情	详情
(XXII)	17414	methyl trifluoromethane sulfonate; methyl trifluoromethanesulfonate	333-27-7	C₂H₃F₃O₃S	详情	详情
(XXII)	45233	methyl trifluoromethanesulfonate		C₂H₃F₃O₃S	详情	详情

Extended Information