Triethylamine → 3-Ethoxy-3-oxo-2-phenylpropanoic acid

HRID 1474069

반응식

HRID 1474069 반응식
[CH2:1]([O:3][C:4](=[O:15])[CH:5]([C:9]1[CH:14]=[CH:13][CH:12]=[CH:11][CH:10]=1)[C:6]([OH:8])=[O:7])[CH3:2].C(Cl)(=O)C(Cl)=O.[Cl:22][C:23]1[N:28]=[CH:27][C:26]([CH2:29][NH:30][C:31]2[CH:36]=[CH:35][CH:34]=[CH:33][N:32]=2)=[CH:25][CH:24]=1.C(N(CC)CC)C>ClCCl.CN(C)C=O>[CH2:1]([O:3][C:4](=[O:15])[CH:5]([C:9]1[CH:14]=[CH:13][CH:12]=[CH:11][CH:10]=1)[C:6]([OH:8])=[O:7])[CH3:2].[CH2:1]([O:3][C:4](=[O:15])[CH:5]([C:9]1[CH:14]=[CH:13][CH:12]=[CH:11][CH:10]=1)[C:6]([N:30]([CH2:29][C:26]1[CH:27]=[N:28][C:23]([Cl:22])=[CH:24][CH:25]=1)[C:31]1[CH:36]=[CH:35][CH:34]=[CH:33][N:32]=1)=[O:8])[CH3:2]

참가 물질

8

반응물 4

HCID 8471TriethylamineHCID 65578Oxalyl chloride2회HCID 27299033-Ethoxy-3-oxo-2-phenylpropanoic acid2회HCID 82676215HCID 82676215, 화합물

생성물 2

HCID 27299033-Ethoxy-3-oxo-2-phenylpropanoic acidHCID 86649152N-[(6-chloro-3-pyridinyl)methyl]-2-phenyl-N-(2-pyridinyl)malonamic acid ethyl ester

시약·촉매·용매 2

HCID 6228Dimethylformamide촉매2회HCID 6344Dichloromethane용매3회

실험 절차

2-Phenylmalonic acid monoethyl ester was prepared following the procedure in Journal of Organic Chemistry 2000, 65, 5834-5836. 2-Phenylmalonic acid monoethyl ester (1.02 g, 5.0 mmol) was dissolved in anhydrous dichloromethane (10 mL), and oxalyl chloride (0.52 mL, 6.0 mmol) was added, followed by one drop of N,N-dimethylformamide. The reaction mixture was stirred for 30 min, then concentrated, redissolved in anhydrous dichloromethane (5 mL) and added to a solution of 6-chloro-N-2-pyridinyl-3-pyridinemethanamine (i.e. the product of Example 3, Step A) (1.1 g, 5.0 mmol) and triethyl amine (0.83 mL, 6.0 mmol) in anhydrous dichloromethane (5 mL) at 0° C. The stirred reaction mixture was allowed to warm to room temperature over 30 min. The reaction mixture was poured onto a silica gel cartridge (Bond Elute manufactured by Varian) and purified using a gradient of 0-50% ethyl acetate/hexanes. A mixture of desired product and starting amine was isolated (1.3 g of 33 mol % recovered amine/67 mol % desired product). 2-Phenylmalonic acid monoethyl ester (0.54 g, 2.6 mmol) was dissolved in anhydrous dichloromethane (3 mL), and oxalyl chloride (0.26 mL, 3.0 mmol) was added, followed by one drop of N,N-dimethylformamide. The reaction mixture was stirred until gas evolution ceased and then concentrated, redissolved in anhydrous dichloromethane (3 mL) and added to the mixture of recovered amine and desired product isolated previously. The reaction mixture was stirred for 30 min and then concentrated, and the crude residue was chromatographed as already described to give the title compound as a solid (0.9 g).

후처리

  1. concentrationconcentrated
  2. dissolutionredissolved in anhydrous dichloromethane (5 mL)
  3. customThe stirred reaction mixture
  4. additionThe reaction mixture was poured onto a silica gel cartridge (Bond Elute manufactured by Varian)
  5. custompurified
  6. additionA mixture of desired product
  7. customwas isolated
  8. custom(1.3 g of 33 mol % recovered amine/67 mol % desired product)
  9. stirringThe reaction mixture was stirred until gas evolution
  10. concentrationconcentrated
  11. dissolutionredissolved in anhydrous dichloromethane (3 mL)
  12. additionadded to the mixture of recovered amine and desired product
  13. customisolated previously
  14. stirringThe reaction mixture was stirred for 30 min
  15. concentrationconcentrated
  16. customthe crude residue was chromatographed

출처 및 근거

ORD 기록
ord-e7eb625c607f4bfd8144dee1e6db042a
출처 데이터셋
uspto-grants-2015_04
특허 번호
US09018220B2

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