Piconol → Pyrrolidine-1-carboxylic acid 4-(pyridin-2-ylmethoxycarbonylamino)-cyclohexylmethyl ester

HRID 68488

반응식

HRID 68488 반응식
[N:1]1[CH:6]=[CH:5][CH:4]=[CH:3][C:2]=1[CH2:7][OH:8].C1N=CN([C:14](N2C=NC=C2)=[O:15])C=1.[NH2:21][CH:22]1[CH2:27][CH2:26][CH:25]([CH2:28][O:29][C:30]([N:32]2[CH2:36][CH2:35][CH2:34][CH2:33]2)=[O:31])[CH2:24][CH2:23]1>C1COCC1.O>[N:1]1[CH:6]=[CH:5][CH:4]=[CH:3][C:2]=1[CH2:7][O:8][C:14]([NH:21][CH:22]1[CH2:27][CH2:26][CH:25]([CH2:28][O:29][C:30]([N:32]2[CH2:36][CH2:35][CH2:34][CH2:33]2)=[O:31])[CH2:24][CH2:23]1)=[O:15]

참가 물질

6

반응물 3

HCID 11474PiconolHCID 682631,1'-CarbonyldiimidazoleHCID 66837809Pyrrolidine-1-carboxylic acid 4-amino-cyclohexylmethyl ester

생성물 1

HCID 66837792Pyrrolidine-1-carboxylic acid 4-(pyridin-2-ylmethoxycarbonylamino)-cyclohexylmethyl ester수율 43%

시약·촉매·용매 2

HCID 962Water용매HCID 8028Tetrahydrofuran용매

실험 절차

To a solution of pyrrolidine-1-carboxylic acid 4-oxo-cyclohexylmethyl ester (2 mmol) in ethanol (10 mL) was added hydroxylamine (10 mmol) and the mixture was refluxed for 5 hours. The reaction mixture was concentrated under reduced pressure, and the residue was dissolved in ethyl acetate and washed with water. The organic layer was dried over anhydrous magnesium sulfate, filtered and concentrated under reduced pressure to provide pyrrolidine-1-carboxylic acid 4-hydroxyimino-cyclohexylmethyl ester. Pyrrolidine-1-carboxylic acid 4-hydroxyimino-cyclohexylmethyl ester was dissolved in a 2N ammonia methanol solution (10 mL) and then Raney nickel was added. After 12 hours stirring under hydrogen atmosphere, the reaction mixture was filtered and concentrated under reduced pressure to provide pyrrolidine-1-carboxylic acid 4-amino-cyclohexylmethyl ester. To a solution of pyridine-2-yl-methanol (2 mmol) in THF (10 mL) was added CDI (2 mmol). After 2 h stirring at room temperature, pyrrolidine-1-carboxylic acid 4-amino-cyclohexylmethyl ester was added and the resulting mixture was stirred for additional 2 hours at 60° C. The reaction mixture was diluted with water, followed by few times of extraction with methylene chloride. The combined organic layer was dried over anhydrous magnesium sulfate, filtered and concentrated under reduced pressure. The residue was purified by column chromatography (silica gel, ethyl acetate), thereby completing the preparation of a target compound (310 mg, 43% yield).

후처리

  1. stirringthe resulting mixture was stirred for additional 2 hours at 60° C
  2. extractionfollowed by few times of extraction with methylene chloride
  3. dry with materialThe combined organic layer was dried over anhydrous magnesium sulfate
  4. filtrationfiltered
  5. concentrationconcentrated under reduced pressure
  6. customThe residue was purified by column chromatography (silica gel, ethyl acetate)

출처 및 근거

ORD 기록
ord-a4630a4b457b41f79f7be14a654e4d39
출처 데이터셋
uspto-grants-2014_09
특허 번호
US08822463B2

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