4-Methylmorpholine → [N-tert-butoxycarbonyl-2-(3-pyridyl)thiazolidine-4-carbonyl]-L-leucine methyl ester

HRID 704423ノート

反応式

HRID 704423 の反応式
[C:1]([O:5][C:6]([N:8]1[CH:12]([C:13]([OH:15])=O)[CH2:11][S:10][CH:9]1[C:16]1[CH:17]=[N:18][CH:19]=[CH:20][CH:21]=1)=[O:7])([CH3:4])([CH3:3])[CH3:2].Cl.[CH3:23][O:24][C:25](=[O:32])[C@H:26]([CH2:28][CH:29]([CH3:31])[CH3:30])[NH2:27].ON1C2C=CC=CC=2N=N1.CN1CCOCC1.C1(N=C=NC2CCCCC2)CCCCC1>O1CCCC1>[CH3:23][O:24][C:25](=[O:32])[C@H:26]([CH2:28][CH:29]([CH3:31])[CH3:30])[NH:27][C:13]([CH:12]1[CH2:11][S:10][CH:9]([C:16]2[CH:17]=[N:18][CH:19]=[CH:20][CH:21]=2)[N:8]1[C:6]([O:5][C:1]([CH3:2])([CH3:3])[CH3:4])=[O:7])=[O:15]

参加物

7

反応物 5

HCID 79724-MethylmorpholineHCID 10868DicyclohexylcarbodiimideHCID 757711-HydroxybenzotriazoleHCID 2723695Leucine methyl ester hydrochlorideHCID 14772789N-tert-butoxycarbonyl-2-(3-pyridyl)thiazolidine-4-carboxylic acid

生成物 1

HCID 57112286[N-tert-butoxycarbonyl-2-(3-pyridyl)thiazolidine-4-carbonyl]-L-leucine methyl ester収率 98.5%

試薬・触媒・溶媒 1

HCID 8028Tetrahydrofuran溶媒

実験手順

To a solution of 600 mg of N-tert-butoxycarbonyl-2-(3-pyridyl)thiazolidine-4 carboxylic acid in 5 ml of tetrahydrofuran, there were added, at 4° C. or below, 350 mg of L-leucine methyl ester hydrochloride, 390 mg of 1-hydroxybenzotriazole, 190 mg of N-methylmorpholine and 440 mg of dicyclohexylcarbodiimide, in that order, and the mixture was stirred overnight in an icehouse. The resultant precipitate was filtered off, the filtrate was concentrated under reduced pressure, 50 ml of ethyl acetate was added, the insoluble matter was filtered off, and the filtrate was washed in sequence with 0.5M aqueous citric acid, water, saturated aqueous solution of sodium hydrogen carbonate and water, dried over anhydrous sodium sulfate and concentrated under reduced pressure to give 830 mg of oily [N-tert-butoxycarbonyl-2-(3-pyridyl)thiazolidine-4-carbonyl]-L-leucine methyl ester. Trifluoroacetic acid (3 ml) was added to 800 mg of the thus obtained compound with ice cooling, and the mixture was stirred at room temperature for 3 hours. The reaction mixture was concentrated under reduced pressure, 10 ml of ethyl acetate was added and the solution was again concentrated under reduced pressure. The residue was dissolved in 10 ml of ethyl acetate, 3 ml of 2.2N hydrogen chloride solution in dioxane was added with ice colling, and the mixture was allowed to stand overnight in an icehouse. The resultant crystals were collected by filtration, washed with ethyl acetate and dried to give 510 mg of [2-(3-pyridyl)thiazolidine-4-carbonyl]-L-leucine methyl ester dihydrochloride. Melting point 97°-100° C.

後処理

  1. filtrationThe resultant precipitate was filtered off
  2. concentrationthe filtrate was concentrated under reduced pressure, 50 ml of ethyl acetate
  3. additionwas added
  4. filtrationthe insoluble matter was filtered off
  5. washthe filtrate was washed in sequence with 0.5M aqueous citric acid, water, saturated aqueous solution of sodium hydrogen carbonate and water
  6. dry with materialdried over anhydrous sodium sulfate
  7. concentrationconcentrated under reduced pressure

出典と根拠

ORDレコード
ord-85cd902eebce46728513c5d0cf5760cb
出典データセット
uspto-grants-1991_01
特許番号
US04987132

反応ノート

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