(2S)-1,2-propanediol -Drug Synthesis Database

【结构式】

【分子编号】19242

【品名】(2S)-1,2-propanediol

【CA登记号】4254-15-3

【分子式】C₃H₈O₂

【分子量】76.09532

【元素组成】C 47.35% H 10.6% O 42.05%

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：(XVII)

3) The catalytic hydrogenation of (S)-glycidol (XVI) over Pd/C gives the (R)-1,2-propanediol (XVII), which is esterified with diethyl carbonate (XVIII)/NaOEt, yielding the cyclic carbonate (XIX). The reaction of (XIX) with adenine (V) by means of NaOH in DMF affords 9-[2(R)-hydroxypropyl]adenine (VII), which is condensed with tosyloxymethylphosphonic acid diethyl ester (XX) by means of lithium tert-butoxide in THF, giving 9-[2(R)-(diethoxyphosphorylmethoxy)propyl]adenine (XXI). Finally, this compound is hydrolyzed with bromotrimethylsilane as before. Compound (XX) is obtained by reaction of diethyl phosphite (XXII) with paraformaldehyde, yielding hydroxy- methylphosphonic acid diethyl ester (XXIII), which is finally tosylated as usual.

参考文献中间体

合成目标

【1】 Leone-Bay, A.; et al.; 4-(4-Salicyloylaminophenyl)butyric acid as a novel oral delivery agent for recombinant human growth hormone. 211th ACS Natl Meet (March 24-28, New Orleans) 1996, Abst MEDI 006.
【2】 Schultze, L.M.; Chapman, H.H.; Dubree, N.J.P.; et al.; Practical synthesis of the anti-HIV drug, PMPA. Tetrahedron Lett 1998, 39, 14, 1853.
【3】 Sorbera, L.A.; Castañer, J.; (R)-PMPA and Bis(POC)PMPA. Drugs Fut 1998, 23, 12, 1279.

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)	10343	9H-Purin-6-amine; 9H-Purin-6-ylamine; Adenine	73-24-5	C₅H₅N₅	详情	详情
(VII)	19232	(2S)-1-(6-amino-9H-purin-9-yl)-2-propanol		C₈H₁₁N₅O	详情	详情
(XVI)	19241	(2S)oxiranylmethanol	60456-23-7	C₃H₆O₂	详情	详情
(XVII)	19242	(2S)-1,2-propanediol	4254-15-3	C₃H₈O₂	详情	详情
(XVIII)	17470	diethyl carbonate; diethylcarbonate	105-58-8	C₅H₁₀O₃	详情	详情
(XIX)	19244	(4S)-4-methyl-1,3-dioxolan-2-one		C₄H₆O₃	详情	详情
(XX)	12702	(diethoxyphosphoryl)methyl 4-methylbenzenesulfonate	31618-90-3	C₁₂H₁₉O₆PS	详情	详情
(XXI)	19246	diethyl [[(1S)-2-(6-amino-9H-purin-9-yl)-1-methylethyl]oxy]methylphosphonate		C₁₃H₂₂N₅O₄P	详情	详情
(XXII)	12714	diethyl phosphonate; diethyl phosphite	762-04-9	C₄H₁₁O₃P	详情	详情
(XXIII)	19248	diethyl hydroxymethylphosphonate	3084-40-0	C₅H₁₃O₄P	详情	详情

合成路线2

该中间体在本合成路线中的序号：(IV)

Treatment of (S)-glycidol (I) with triphenylmethyl chloride (Ph3CCl) in pyridine affords O-triphenylmethylglicydyl ether (II), which is then reduced with LiAlH4 in THF to provide alcohol (III). Hydrogenolysis of (III) over Pd/C in MeOH gives 1,2-propandiol (IV), which is then mesylated by means of methanesulfonyl chloride (MsCl) and Et3N in CH2Cl2 to furnish 1-mesyloxy-2-propanol (V). Treatment of tropane (VI) with a refluxing mixture of dioxane/H2O yields carboxylic acid (VII), which is converted into acid chloride (VIII) by means of phosphorus oxychloride (POCl3). Coupling of alcohol (V) with acid chloride (VIII) and Et3N in CH2Cl2 gives tropane derivative (IX), which is finally converted into the target compound by fluorination with tetrabutylammonium fluoride (TBAF) in THF.

参考文献中间体

合成目标

【1】 Xing, D.; Keil, R.; Chen, P.; et al.; Synthesis, biodistribution, and primate imaging of fluorine-18 labeled 2 beta-carbo-1'-fluoro-2-propoxy-3beta-(4-chlorophenyl)tropanes. Ligands for the imaging of dopamine transporters by positron emission tomography. J Med Chem 2000, 43, 4, 639.

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)	19241	(2S)oxiranylmethanol	60456-23-7	C₃H₆O₂	详情	详情
(II)	41006	(2S)-oxiranylmethyl trityl ether; (2S)-2-[(trityloxy)methyl]oxirane		C₂₂H₂₀O₂	详情	详情
(III)	44832	(2R)-1-(trityloxy)-2-propanol		C₂₂H₂₂O₂	详情	详情
(IV)	19242	(2S)-1,2-propanediol	4254-15-3	C₃H₈O₂	详情	详情
(V)	44833	(2R)-1-[[methyl(dimethylene)-lambda(6)-sulfanyl]oxy]-2-propanol		C₆H₁₄O₂S	详情	详情
(VI)	44837	(1R)-1-methyl-2-[[methyl(dimethylene)-lambda(6)-sulfanyl]oxy]ethyl (1S,2S,3S,5R)-3-(4-chlorophenyl)-8-methyl-8-azabicyclo[3.2.1]octane-2-carboxylate		C₂₁H₃₀ClNO₃S	详情	详情
(VII)	44834	methyl (1S,2S,3S,5R)-3-(4-chlorophenyl)-8-methyl-8-azabicyclo[3.2.1]octane-2-carboxylate		C₁₆H₂₀ClNO₂	详情	详情
(VIII)	44835	(1S,2S,3S,5R)-3-(4-chlorophenyl)-8-methyl-8-azabicyclo[3.2.1]octane-2-carboxylic acid		C₁₅H₁₈ClNO₂	详情	详情
(IX)	44836	(1S,2S,3S,5R)-3-(4-chlorophenyl)-8-methyl-8-azabicyclo[3.2.1]octane-2-carbonyl chloride		C₁₅H₁₇Cl₂NO	详情	详情

Extended Information