benzyl (2R)-2-{[4-(benzyloxy)-3,5-dichlorobenzoyl]amino}-3-iodopropanoate -Drug Synthesis Database

【结构式】

【分子编号】61502

【品名】benzyl (2R)-2-{[4-(benzyloxy)-3,5-dichlorobenzoyl]amino}-3-iodopropanoate

【CA登记号】

【分子式】C₂₄H₂₀Cl₂INO₄

【分子量】584.23701

【元素组成】C 49.34% H 3.45% Cl 12.14% I 21.72% N 2.4% O 10.95%

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)

Synthesis of the iodopropionic intermediate (IV) is achieved as follows. The condensation of 4-benzyloxy-3,5-dichlorobenzoic acid (I) with L-serine benzyl ester (II) by means of BOP and TEA in dichloromethane gives the benzoyl-serine (III), which is then converted into the target iodopropionic intermediate (IV) by reaction with MsCl and TEA, followed by treatment with NaI in acetone.

参考文献中间体

合成目标

【1】 Watanabe, H.; Okue, M.; Kobayashi, H.; Kitahara, T.; The first synthesis of kaitocephalin based on the structure revision. Tetrahedron Lett 2002, 43, 5, 861.

中间体序号	中间体编号	品名	分子式	供应商	用于合成
(I)	61500	4-(benzyloxy)-3,5-dichlorobenzoic acid	C₁₄H₁₀Cl₂O₃	详情	详情
(II)	38229	benzyl (2S)-2-amino-3-hydroxypropanoate	C₁₀H₁₃NO₃	详情	详情
(III)	61501	benzyl (2S)-2-{[4-(benzyloxy)-3,5-dichlorobenzoyl]amino}-3-hydroxypropanoate	C₂₄H₂₁Cl₂NO₅	详情	详情
(IV)	61502	benzyl (2R)-2-{[4-(benzyloxy)-3,5-dichlorobenzoyl]amino}-3-iodopropanoate	C₂₄H₂₀Cl₂INO₄	详情	详情

合成路线2

该中间体在本合成路线中的序号：(IV)

The condensation of lactone (V) -prepared from L-proline by the Seebach method- with aldehyde (VI) -prepared from L-serine by the Garner method- by means of LDA in THF gives a mixture of the syn and anti alcohols (VII) and (VIII). The minor compound (VII) is converted into the desired enantiomer by oxidation with DMP, followed by reduction with NaBH4. The treatment of (VIII) with 10% H2SO4 causes an intramolecular transacetalization of the t-butyloxazoline and simultaneous hydrolysis of the dimethyloxazoline. The resulting product is benzylated at the carboxyl group and silylated with Tbdps-Cl to afford the bicyclic oxazolidine (IX). The hydrolysis of (IX) with acetic acid and subsequent protection of the resulting secondary alcohol with Tms-Cl provides the pyrrolidine (X), which is oxidized with MeReO3/urea/H2O2 to give the nitrone (XI). The condensation of (XI) with the iodopropionic intermediate (IV) by means of Zn and CuI in THF/water yields the hydroxylamine (XII), which is reduced with Zn and NH4Cl, and then protected with Cbz-Cl/K2CO3 to afford the carbamate (XIII). The removal of the silyl protecting groups of (XIII) by means of Tms-Cl in methanol provides the diol (XIV), which is selectively oxidized at the primary OH group by means of 4-methoxy-TEMPO and NaClO2 to give the carboxylic acid (XV). Finally, hydrogenolysis of the benzylic protecting groups of (XV) by means of H2 over Pd/C in ethanol/chloroform affords the target kaitocephalin

参考文献中间体

合成目标

【1】 Watanabe, H.; Okue, M.; Kobayashi, H.; Kitahara, T.; The first synthesis of kaitocephalin based on the structure revision. Tetrahedron Lett 2002, 43, 5, 861.

中间体序号	中间体编号	品名	分子式	供应商	用于合成
(IV)	61502	benzyl (2R)-2-{[4-(benzyloxy)-3,5-dichlorobenzoyl]amino}-3-iodopropanoate	C₂₄H₂₀Cl₂INO₄	详情	详情
(V)	33128	(3R,7aS)-3-(tert-butyl)tetrahydro-1H-pyrrolo[1,2-c][1,3]oxazol-1-one	C₁₀H₁₇NO₂	详情	详情
(VI)	61503	benzyl (4S)-4-formyl-2,2-dimethyl-1,3-oxazolidine-3-carboxylate	C₁₄H₁₇NO₄	详情	详情
(VII)	61504	benzyl (4S)-4-[(R)-[(3R)-3-(tert-butyl)-1-oxodihydro-1H-pyrrolo[1,2-c][1,3]oxazol-7(5H)-yl](hydroxy)methyl]-2,2-dimethyl-1,3-oxazolidine-3-carboxylate	C₂₄H₃₄N₂O₆	详情	详情
(VIII)	61505	benzyl (4S)-4-[(S)-[(3R)-3-(tert-butyl)-1-oxodihydro-1H-pyrrolo[1,2-c][1,3]oxazol-7(5H)-yl](hydroxy)methyl]-2,2-dimethyl-1,3-oxazolidine-3-carboxylate	C₂₄H₃₄N₂O₆	详情	详情
(IX)	61506	benzyl (1R,3S)-1-((S)-{[(benzyloxy)carbonyl]amino}{[tert-butyl(diphenyl)silyl]oxy}methyl)-3-(tert-butyl)dihydro-1H-pyrrolo[1,2-c][1,3]oxazole-7a(5H)-carboxylate	C₄₃H₅₂N₂O₆Si	详情	详情
(X)	61507	benzyl (2R)-2-{(1S,2S)-2-{[(benzyloxy)carbonyl]amino}-3-{[tert-butyl(diphenyl)silyl]oxy}-1-[(trimethylsilyl)oxy]propyl}-2-pyrrolidinecarboxylate	C₄₂H₅₄N₂O₆Si₂	详情	详情
(XI)	61508	(2R)-2-[(benzyloxy)carbonyl]-2-{(1S,2S)-2-{[(benzyloxy)carbonyl]amino}-3-{[tert-butyl(diphenyl)silyl]oxy}-1-[(trimethylsilyl)oxy]propyl}-3,4-dihydro-2H-pyrrolium-1-olate	C₄₂H₅₂N₂O₇Si₂	详情	详情
(XII)	61509	benzyl (2R,5R)-5-((2S)-3-(benzyloxy)-2-{[4-(benzyloxy)-3,5-dichlorobenzoyl]amino}-3-oxopropyl)-2-{(1S,2S)-2-{[(benzyloxy)carbonyl]amino}-3-{[tert-butyl(diphenyl)silyl]oxy}-1-[(trimethylsilyl)oxy]propyl}-1-hydroxy-2-pyrrolidinecarboxylate	C₆₆H₇₃Cl₂N₃O₁₁Si₂	详情	详情
(XIII)	61510	dibenzyl (2R,5R)-5-((2S)-3-(benzyloxy)-2-{[4-(benzyloxy)-3,5-dichlorobenzoyl]amino}-3-oxopropyl)-2-{(1S,2S)-2-{[(benzyloxy)carbonyl]amino}-3-{[tert-butyl(diphenyl)silyl]oxy}-1-[(trimethylsilyl)oxy]propyl}-1,2-pyrrolidinedicarboxylate	C₇₄H₇₉Cl₂N₃O₁₂Si₂	详情	详情
(XIV)	61511	dibenzyl (2R,5R)-5-((2S)-3-(benzyloxy)-2-{[4-(benzyloxy)-3,5-dichlorobenzoyl]amino}-3-oxopropyl)-2-((1S,2S)-2-{[(benzyloxy)carbonyl]amino}-1,3-dihydroxypropyl)-1,2-pyrrolidinedicarboxylate	C₅₅H₅₃Cl₂N₃O₁₂	详情	详情
(XV)	61512	(2R,3S)-3-{(2R,5R)-5-((2S)-3-(benzyloxy)-2-{[4-(benzyloxy)-3,5-dichlorobenzoyl]amino}-3-oxopropyl)-1,2-bis[(benzyloxy)carbonyl]pyrrolidinyl}-2-{[(benzyloxy)carbonyl]amino}-3-hydroxypropanoic acid	C₅₅H₅₁Cl₂N₃O₁₃	详情	详情

Extended Information