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【结 构 式】 
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【分子编号】29431 【品名】(4S)-4-benzyl-3-pentanoyl-1,3-oxazolidin-2-one 【CA登记号】 |
【 分 子 式 】C15H19NO3 【 分 子 量 】261.3208 【元素组成】C 68.94% H 7.33% N 5.36% O 18.37% |
合成路线1
该中间体在本合成路线中的序号：(III)The intermediate (R)-formyl amide (IX) was synthesized as follows. Acylation of the lithium anion of (S)-4-benzyl-2-oxazolidinone (I) with valeryl chloride (II) provided acyl oxazolidinone (III). Subsequent diastereoselective benzyloxymethylation of (III) with chloride (IV) and TiCl4 gave benzyl ether (V). Hydrolysis of (V) with lithium peroxide, followed by coupling of the resulting carboxylic acid (VI) with diethylamine in the presence of TBTU yielded diethylamide (VII). Hydrogenolysis of the benzyl group of (VII) using Pearlman's catalyst afforded alcohol (VIII), which was oxidized to aldehyde (IX) by means of Dess-Martin periodinane or NaOCl in the presence of 2,2,6,6-tetramethyl-1-piperidinyloxy radical (TEMPO) to give (IX).
| 【1】 Soucy, F.; et al.; A novel and efficient synthesis of a highly active analogue clasto-lactacystin beta-lactone. J Am Chem Soc 1999, 121, 43, 9967. |
| 【2】 Plamondon, L.; Soucy, F.; Behnke, M.; Roush, W.; Synthesis of clasto-lactacystin beta-lactone and analogs thereof. WO 9909006 . |
| 【3】 Plamondon, L.; Adams, J.; Elliot, P. (ProScript, Inc.); Proteasome inhibitors, ubiquitin pathway inhibitors or agents that interfere with the activation of NF-kappaB via the ubiquitin proteasome pathway to treat inflammatory and autoimmune diseases. WO 9915183 . |
| 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) | 14694 | (S)-4-Benzyl-2-oxazolidinone; (4S)-4-Benzyl-1,3-oxazolan-2-one; (S)-(-)-4-Benzyl-2-oxazolidinone | 90719-32-7 | C10H11NO2 | 详情 | 详情 |
| (II) | 15116 | pentanoyl chloride; valeryl chloride | 638-29-9 | C5H9ClO | 详情 | 详情 |
| (III) | 29431 | (4S)-4-benzyl-3-pentanoyl-1,3-oxazolidin-2-one | C15H19NO3 | 详情 | 详情 | |
| (IV) | 14560 | Benzyl chloromethyl ether; 1-[(chloromethoxy)methyl]benzene | 3587-60-8 | C8H9ClO | 详情 | 详情 |
| (V) | 37794 | (4S)-4-benzyl-3-[(2R)-2-[(benzyloxy)methyl]pentanoyl]-1,3-oxazolidin-2-one | C23H27NO4 | 详情 | 详情 | |
| (VI) | 37795 | (2R)-2-[(benzyloxy)methyl]pentanoic acid | C13H18O3 | 详情 | 详情 | |
| (VII) | 37796 | (2R)-2-[(benzyloxy)methyl]-N,N-diethylpentanamide | C17H27NO2 | 详情 | 详情 | |
| (VIII) | 37797 | (2R)-N,N-diethyl-2-(hydroxymethyl)pentanamide | C10H21NO2 | 详情 | 详情 | |
| (IX) | 37798 | (2R)-N,N-diethyl-2-formylpentanamide | C10H19NO2 | 详情 | 详情 |
合成路线2
该中间体在本合成路线中的序号：(III)Condensation of pentanoyl chloride (I) with (S)-4-benzyl-2-oxazolidinone (II) in the presence of n-butyllithium afforded the chiral N-acyl oxazolidinone (III). Subsequent asymetric alkylation of (III) with 1-bromo-2-butyne (IV) using LDA as the base produced the alkylated diastereoisomer (V). The chiral auxiliary oxazolidinone was finally removed by hydrolysis with lithium hydroperoxide to afford the required (R)-carboxylic acid.
| 【1】 Hauck, R.-S.; Elmazar, M.M.E.; Nau, H.; Bojic, U.; VPA-analogous antiepileptics. DE 4231085; US 5786380; WO 9406743 . |
| 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) | 15116 | pentanoyl chloride; valeryl chloride | 638-29-9 | C5H9ClO | 详情 | 详情 |
| (II) | 14694 | (S)-4-Benzyl-2-oxazolidinone; (4S)-4-Benzyl-1,3-oxazolan-2-one; (S)-(-)-4-Benzyl-2-oxazolidinone | 90719-32-7 | C10H11NO2 | 详情 | 详情 |
| (III) | 29431 | (4S)-4-benzyl-3-pentanoyl-1,3-oxazolidin-2-one | C15H19NO3 | 详情 | 详情 | |
| (IV) | 29428 | 1-bromo-2-butyne | 3355-28-0 | C4H5Br | 详情 | 详情 |
| (V) | 29432 | (4S)-4-benzyl-3-[(2R)-2-propyl-4-hexynoyl]-1,3-oxazolidin-2-one | C19H23NO3 | 详情 | 详情 |
合成路线3
该中间体在本合成路线中的序号：(III)Treatment of S-4-benzyl-2-oxazolidinone (II) with n-butyllithium, followed by acylation with valeroyl chloride (I) afforded the N-valeroyloxazolidinone (III). Subsequent alkylation of (III) with isopropyl triflate (V), prepared from isopropyl alcohol (IV) and trifluoromethanesulfonic anhydride, in the presence of LDA produced the (4S,2'R)-2-isopropylvaleroyl derivative (VI). Hydrolysis of (VI) using lithium peroxide yielded the chiral carboxylic acid (VII), which was converted to the corresponding acid chloride (VIII) by treatment with oxalyl chloride. Finally, reaction of (VIII) with ammonia furnished the title amide.
| 【1】 Yagen, B.; Bialer, M.; Spigelstein, O. (Yissum Research Development Co.); Propylisopropyl acetic acid and propylisopropyl acetamide stereoisomers, a method for their synthesis and pharmaceutical compsns. containing them. WO 9954282 . |
| 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) | 14694 | (S)-4-Benzyl-2-oxazolidinone; (4S)-4-Benzyl-1,3-oxazolan-2-one; (S)-(-)-4-Benzyl-2-oxazolidinone | 90719-32-7 | C10H11NO2 | 详情 | 详情 |
| (II) | 15116 | pentanoyl chloride; valeryl chloride | 638-29-9 | C5H9ClO | 详情 | 详情 |
| (III) | 29431 | (4S)-4-benzyl-3-pentanoyl-1,3-oxazolidin-2-one | C15H19NO3 | 详情 | 详情 | |
| (IV) | 19250 | 2-propanol | 67-63-0 | C3H8O | 详情 | 详情 |
| (V) | 35062 | isopropyl trifluoromethanesulfonate | C4H7F3O3S | 详情 | 详情 | |
| (VI) | 35063 | (4S)-4-benzyl-3-[(2R)-2-isopropylpentanoyl]-1,3-oxazolidin-2-one | C18H25NO3 | 详情 | 详情 | |
| (VII) | 35064 | (2R)-2-isopropylpentanoic acid | C8H16O2 | 详情 | 详情 | |
| (VIII) | 35065 | (2R)-2-isopropylpentanoyl chloride | C8H15ClO | 详情 | 详情 |