4-Methylmorpholine → N-[[trans 3-(acetylthiomethyl)-2-oxo-1-aza-cyclodecan-10-yl]-carbonyl]-trans 4-hydroxy-L-proline ethyl ester

HRID 21976

反応式

HRID 21976 の反応式
[C:1]([S:4][CH2:5][C@H:6]1[CH2:15][CH2:14][CH2:13][CH2:12][CH2:11][CH2:10][C@H:9]([C:16]([OH:18])=O)[NH:8][C:7]1=[O:19])(=[O:3])[CH3:2].ON1C2C=CC=CC=2N=N1.CN1CCOCC1.Cl.[CH2:38]([O:40][C:41](=[O:48])[C@@H:42]1[CH2:46][C@@H:45]([OH:47])[CH2:44][NH:43]1)[CH3:39].Cl.CN(CCCN=C=NCC)C>C(Cl)Cl>[CH2:38]([O:40][C:41](=[O:48])[C@@H:42]1[CH2:46][C@@H:45]([OH:47])[CH2:44][N:43]1[C:16]([C@@H:9]1[NH:8][C:7](=[O:19])[C@@H:6]([CH2:5][S:4][C:1](=[O:3])[CH3:2])[CH2:15][CH2:14][CH2:13][CH2:12][CH2:11][CH2:10]1)=[O:18])[CH3:39]

参加物

7

反応物 5

HCID 79724-MethylmorpholineHCID 757711-HydroxybenzotriazoleHCID 27239391,3-Propanediamine, N'-(ethylcarbonimidoyl)-N,N-dimethyl-, monohydrochlorideHCID 12709304Ethyl trans-4-hydroxy-L-prolinate hydrochlorideHCID 86747202trans 3-(Acetylthiomethyl)-2-oxo-1-azacyclodecane-10-carboxylic acid

生成物 1

HCID 86747211N-[[trans 3-(acetylthiomethyl)-2-oxo-1-aza-cyclodecan-10-yl]-carbonyl]-trans 4-hydroxy-L-proline ethyl ester

試薬・触媒・溶媒 1

HCID 6344Dichloromethane溶媒2 回

反応条件

温度
0 °C

実験手順

The enantiomer of trans 3-(acetylthiomethyl)-2-oxo-1-azacyclodecane-10-carboxylic acid of Example 16 (0.23 g, 0.80 mmol), 1-hydroxybenzotriazole (0.11 g, 0.80 mmol), 4-methylmorpholine (0.22 mL, 2.0 mmol), and L-hydroxyproline ethyl ester hydrochloride (0.16 g, 0.80 mmol) are dissolved in methylene chloride (5.0 mL), and the reaction is cooled to 0° C. To this solution is added N-[dimethylaminopropyl]-N'-ethylcarbodiimide hydrochloride (0.31 g, 1.60 mmol), and the reaction is allowed to warm up to room temperature and stirred overnight. The reaction is diluted with more methylene chloride, and the organic layer is washed with 1N hydrochloric acid, saturated sodium bicarbonate, dried (MgSO4), and the solvent is evaporated. The product is purified by silica gel chromatography (80% ethyl acetate/hexane) to give N-[[trans 3-(acetylthiomethyl)-2-oxo-1-azacyclodecan-10-yl]-carbonyl]-trans 4-hydroxy-L-proline ethyl ester as a single enantiomer, [α]D +5.73° (c=4.1 mg/ml,CH2Cl2) which is assigned the 3R, 10S configuration.

後処理

  1. temperatureto warm up to room temperature
  2. washthe organic layer is washed with 1N hydrochloric acid, saturated sodium bicarbonate
  3. dry with materialdried (MgSO4)
  4. customthe solvent is evaporated
  5. customThe product is purified by silica gel chromatography (80% ethyl acetate/hexane)

出典と根拠

ORDレコード
ord-175b988347ed4cf4a7fea5a4a1058771
出典データセット
uspto-grants-1995_06
特許番号
US05426103

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