1-Ethyl-3-(3'-dimethylaminopropyl)carbodiimide → [(R)-2-((S)-3-fluoropyrrolidin-1-yl)-1-methyl-2-oxo-ethyl]-carbamic acid tert-butyl ester

HRID 246089ノート

反応式

HRID 246089 の反応式
[C:1]([O:5][C:6]([NH:8][C@H:9]([CH3:13])[C:10]([OH:12])=O)=[O:7])([CH3:4])([CH3:3])[CH3:2].CN(C)CCCN=C=NCC.OC1C2N=NNC=2C=CC=1.Cl.[F:36][C@H:37]1[CH2:41][CH2:40][NH:39][CH2:38]1.C(N(CC)C(C)C)(C)C>CN(C=O)C.C(OCC)(=O)C>[C:1]([O:5][C:6](=[O:7])[NH:8][C@H:9]([CH3:13])[C:10]([N:39]1[CH2:40][CH2:41][C@H:37]([F:36])[CH2:38]1)=[O:12])([CH3:2])([CH3:3])[CH3:4]

参加物

8

反応物 5

HCID 159081-Ethyl-3-(3'-dimethylaminopropyl)carbodiimideHCID 81531DiisopropylethylamineHCID 637606BOC-D-alanineHCID 16217739(s)-3-Fluoropyrrolidine hydrochlorideHCID 178418300HCID 178418300、化合物

生成物 1

HCID 71279860[(R)-2-((S)-3-fluoropyrrolidin-1-yl)-1-methyl-2-oxo-ethyl]-carbamic acid tert-butyl ester収率 94.2%

試薬・触媒・溶媒 2

HCID 6228Dimethylformamide溶媒HCID 8857Ethyl Acetate溶媒

実験手順

(R)-2-tert-Butoxycarbonylamino-propionic acid (1.0 g, 5.3 mmol), 1-(3-(dimethylamino)-propyl)-3-ethylcarbodiimide (2.33 g, 12.2 mmol) and hydroxybenzotriazole (1.64 g, 12.2 mmol) were dissolved in DMF (50 ml). (S)-3-Fluoropyrrolidine hydrochloride (1.66 g, 13.2 mmol) and N,N-diisopropylethylamine (2.95 ml, 16.9 mmol) were added and the mixture was stirred at room temperature for 16 h. Ethyl acetate was added and the solution was washed with 10% citric acid solution three times. The organic layer was washed with sodium bicarbonate solution which was then back-extracted with ethyl acetate four times. The combined organic layers were then washed further with lithium chloride solution, sodium chloride solution, and dried over magnesium sulfate. Concentration of the solution gave 1.3 g (94%) of [(R)-2-((S)-3-fluoro-pyrrolidin-1-yl)-1-methyl-2-oxo-ethyl]-carbamic acid tert-butyl ester.

後処理

  1. washthe solution was washed with 10% citric acid solution three times
  2. washThe organic layer was washed with sodium bicarbonate solution which
  3. extractionwas then back-extracted with ethyl acetate four times
  4. washThe combined organic layers were then washed further with lithium chloride solution, sodium chloride solution
  5. dry with materialdried over magnesium sulfate

出典と根拠

ORDレコード
ord-e45ebdc4250f41aa8857fa84ecc243f6
出典データセット
uspto-grants-2014_02
特許番号
US08658646B2

反応ノート

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