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Ammonium Hydroxide → 3N-Benzyloxycarbonyl 3-Amino-2,2-dimethylpropanamide

HRID 1695023
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HRID 1695023 반응식
C(N1C=CN=C1)([N:3]1C=CN=C1)=O.[CH2:13]([O:20][C:21]([NH:23][CH2:24][C:25]([CH3:30])([CH3:29])[C:26](O)=[O:27])=[O:22])[C:14]1[CH:19]=[CH:18][CH:17]=[CH:16][CH:15]=1.[NH4+].[OH-]>O1CCCC1.O>[CH2:13]([O:20][C:21]([NH:23][CH2:24][C:25]([CH3:30])([CH3:29])[C:26]([NH2:3])=[O:27])=[O:22])[C:14]1[CH:19]=[CH:18][CH:17]=[CH:16][CH:15]=1
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참가 물질

6

반응물 3

HCID 14923Ammonium HydroxideHCID 682631,1'-CarbonyldiimidazoleHCID 145510103-(((Benzyloxy)carbonyl)amino)-2,2-dimethylpropanoic acid

생성물 1

HCID 230788763N-Benzyloxycarbonyl 3-Amino-2,2-dimethylpropanamide수율 82.3%

시약·촉매·용매 2

HCID 962Water용매
HCID 8028
Tetrahydrofuran
용매

실험 절차

11.6 g of sodium periodate (54.2 mmol) and 0.2 g of ruthenium trichloride (0.96 mmol) were added to a solution of 4.6 g of 3-benzyloxycarbonylamino-2,2-di(methyl)propanol obtained in Reference Example (2a) (19.4 mmol) in a mixed solvent of carbon tetrachloride (40 ml), acetonitrile and water (40 ml), and the mixture was stirred at room temperature for 16 hours. 11.6 g of sodium periodate (54.2 mmol) and 0.2 g of ruthenium trichloride (0.96 mmol) were added to the reaction mixture, and the mixture was further stirred at room temperature for three days. The reaction mixture was diluted with water, followed by extraction with ethyl acetate. Then, the organic layer was dried over magnesium sulfate. After filtration, 300 ml of a saturated potassium carbonate aqueous solution was added to the residue, followed by washing with ethyl acetate. The aqueous layer was adjusted to pH 1 with concentrated hydrochloric acid, followed by extraction with ethyl acetate. Then, the organic layer was washed with brine and dried over anhydrous magnesium sulfate. After filtration, the solvent was evaporated under reduced pressure to obtain 3.16 g of crude 3-benzyloxycarbonylamino-2,2-di(methyl)propionic acid. 3.0 g of 1,1′-carbonylbis-1H-imidazole (18.5 mmol) was added to a solution of 3.1 g of the crude 3-benzyloxycarbonylamino-2,2-di(methyl)propionic acid obtained above (12.3 mmol) in tetrahydrofuran (20 ml), and the mixture was stirred at room temperature for one hour. 20 ml of a 28% ammonia aqueous solution (914 mmol) was added to the reaction mixture, and the mixture was further stirred at room temperature for one hour. The reaction mixture was diluted with water, followed by extraction with ethyl acetate. Then, the organic layer was washed with a 1 M hydrochloric acid aqueous solution and brine and dried over magnesium sulfate. After filtration, 300 ml of a saturated potassium carbonate aqueous solution was added to the residue, followed by washing with ethyl acetate. The aqueous layer was adjusted to pH 1 with concentrated hydrochloric acid, followed by extraction with ethyl acetate. Then, the organic layer was washed with brine and dried over anhydrous magnesium sulfate. After filtration, the solvent was evaporated under reduced pressure, and the residue was purified by silica gel column chromatography (elution solvent:ethyl acetate/n-hexane=2/1-3/1) to obtain 2.54 g of the title compound (yield: 54%).

후처리

  1. stirringthe mixture was further stirred at room temperature for one hour
  2. extractionfollowed by extraction with ethyl acetate
  3. washThen, the organic layer was washed with a 1 M hydrochloric acid aqueous solution and brine
  4. dry with materialdried over magnesium sulfate
  5. filtrationAfter filtration, 300 ml of a saturated potassium carbonate aqueous solution
  6. additionwas added to the residue
  7. washby washing with ethyl acetate
  8. extractionfollowed by extraction with ethyl acetate
  9. washThen, the organic layer was washed with brine
  10. dry with materialdried over anhydrous magnesium sulfate
  11. filtrationAfter filtration
  12. customthe solvent was evaporated under reduced pressure
  13. customthe residue was purified by silica gel column chromatography (elution solvent:ethyl acetate/n-hexane=2/1-3/1)

출처 및 근거

ORD 기록
ord-7b031967bd7c4954998e0246a7cd1695
출처 데이터셋
uspto-grants-2012_04
DOI
10.6084/m9.figshare.5104873.v1
특허 번호
US08158790B2

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