N-乙基吗啉 → L-脯氨酸叔丁酯

HRID 54055

反应方程式

HRID 54055 反应方程式
C(OC([NH:11][C@H:12]([C:17]([OH:19])=[O:18])[CH2:13][CH:14]([CH3:16])C)=O)C1C=CC=CC=1.C(N1CCOCC1)C.ClC(O[CH2:32][CH:33]([CH3:35])[CH3:34])=O>O1CCCC1>[C:33]([O:19][C:17](=[O:18])[C@@H:12]1[CH2:13][CH2:14][CH2:16][NH:11]1)([CH3:35])([CH3:34])[CH3:32]

参与物

5

反应物 3

HCID 7525N-乙基吗啉2 次HCID 62365氯甲酸异丁酯HCID 74840N-苄氧羰基-L-亮氨酸

产物 1

HCID 6453108L-脯氨酸叔丁酯

试剂、催化剂与溶剂 1

HCID 8028四氢呋喃溶剂2 次

反应条件

温度
-15 °C

实验过程

0.566 g (2.134 mmol) of N-(benzyloxycarbonyl)-L-leucine was taken up in 15 ml of tetrahydrofuran and cooled to -15° C. 0.245 g (2.134 mmol) of N-ethylmorpholine and 0.291 g (2.134mmol) of isobutyl chloroformate were added. After 5 minutes the tetrahydrofuran solution prepared as described in the previous paragraph was added, followed by 0.451 g (4.27 mmol) of N-ethylmorpholine. The mixture was stirred at room temperature for 10 hours, the solvent was then removed by evaporation and the residue was partitioned between ethyl acetate and water. The ethyl acetate solution was washed with saturated sodium bicarbonate solution and with saturated sodium chloride solution and then dried over anhydrous sodium sulphate. The solvent was removed under a vacuum to give 1.5 g of crude N-[3(S)-[[N-(benzyloxycarbonyl)-L-leucyl]amino]-2-(R and S)-hydroxy-4-phenylbutyl]-L-proline tert.butyl ester as an oil. The two isomers were separated by chromatography on silica gel using 50% n-hexane in ethyl acetate for the elution. There were obtained 180 mg of isomer 1 of N-[3(S)-[[N-(benzyloxycarbonyl)-L-leucyl]amino]-2(R or S)-hydroxy-4-phenylbutyl]-L-proline tert.butyl ester as a crystalline material; Rf (System A): 0.34; MS: m/e 582 [M+H]+, and 70 mg of isomer 2 as a crystalline material; Rf (System A): 0.28; MS: m/e 582 [M+H]+.

后处理

  1. additionwas added
  2. customthe solvent was then removed by evaporation
  3. customthe residue was partitioned between ethyl acetate and water
  4. washThe ethyl acetate solution was washed with saturated sodium bicarbonate solution and with saturated sodium chloride solution
  5. dry with materialdried over anhydrous sodium sulphate
  6. customThe solvent was removed under a vacuum

来源与证据

ORD记录
ord-fa00b1b67f064d65bdc503f2fea43ad1
来源数据集
uspto-grants-1997_04
专利号
US05620987

关联笔记

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