1,2-Dichloroethane → Methyl 4-[1,1-difluoro-2-oxo-2-({(1R)-1-[5-(2,2,2-trifluoroethoxy)pyridin-2-yl]ethyl}amino)ethyl]-benzoate

HRID 254737

반응식

HRID 254737 반응식
[F:1][C:2]([F:16])([C:6]1[CH:11]=[CH:10][C:9]([C:12]([O:14][CH3:15])=[O:13])=[CH:8][CH:7]=1)[C:3]([OH:5])=O.[Cl-].[Cl-].[NH3+:19][C@@H:20]([C:22]1[CH:27]=[CH:26][C:25]([O:28][CH2:29][C:30]([F:33])([F:32])[F:31])=[CH:24][NH+:23]=1)[CH3:21].C1C=NC2N(O)N=NC=2C=1.C(Cl)CCl.CCN(C(C)C)C(C)C>C(Cl)Cl>[F:16][C:2]([C:6]1[CH:11]=[CH:10][C:9]([C:12]([O:14][CH3:15])=[O:13])=[CH:8][CH:7]=1)([F:1])[C:3](=[O:5])[NH:19][C@@H:20]([C:22]1[CH:27]=[CH:26][C:25]([O:28][CH2:29][C:30]([F:33])([F:31])[F:32])=[CH:24][N:23]=1)[CH3:21]

참가 물질

7

반응물 5

HCID 111,2-DichloroethaneHCID 81531DiisopropylethylamineHCID 181649HOAtHCID 575412392-(4-(Methoxycarbonyl)phenyl)-2,2-difluoroacetic acidHCID 178462209HCID 178462209, 화합물

생성물 1

HCID 57948474Methyl 4-[1,1-difluoro-2-oxo-2-({(1R)-1-[5-(2,2,2-trifluoroethoxy)pyridin-2-yl]ethyl}amino)ethyl]-benzoate수율 65.2%

시약·촉매·용매 1

HCID 6344Dichloromethane용매2회

실험 절차

To a solution of 0.400 g (1.72 mmol) difluoro[4-(methoxycarbonyl)phenyl]acetic acid in 3.50 ml CH2Cl2 was added 0.560 g (1.90 mmol) 2-[(1R)-1-ammonioethyl]-5-(2,2,2-trifluoroethoxy)pyridinium dichloride, 0.308 g (2.26 mmol) HOAT, 0.433 g (2.26 mmol) EDC, and 0.91 mL (5.21 mmol) DIEA. After 24.0 h at room temperature, the reaction mixture was diluted with CH2Cl2, washed three times with water, and washed with brine. The organic layer was dried over NaSO4, filtered and concentrated in vacuo. Purification by flash chromatography (1×14 cm silica gel, linear gradient 0-30% EtOAc:hexane) afforded 0.485 g (65%) Methyl 4-[1,1-difluoro-2-oxo-2-({(1R)-1-[5-(2,2,2-trifluoroethoxy)pyridin-2-yl]ethyl}amino)ethyl]-benzoate. 1H NMR (CDCl3, 400 MHz) 8.32 (d, 1H, J=2.84 Hz); 8.10 (d, 2H, J=8.05 Hz); 7.93 (br d, 1H, J=5.95 Hz); 7.71 (d, 2H, J=8.25 Hz); 7.28 (d, 1H, J=2.75 Hz); 7.23 (d, 1H, J=17.12 Hz); 5.19 (m, 1H); 4.41 (q, 2H, J=7.87 Hz); 3.93 (d, 3H, J=0.55 Hz); 1.49 (d, 3H, J=6.68). ESMS+1 for C19H17F5N2O4: 433.1.

후처리

  1. washwashed three times with water
  2. washwashed with brine
  3. dry with materialThe organic layer was dried over NaSO4
  4. filtrationfiltered
  5. concentrationconcentrated in vacuo
  6. customPurification by flash chromatography (1×14 cm silica gel, linear gradient 0-30% EtOAc:hexane)

출처 및 근거

ORD 기록
ord-a6dd31a7b36c4dd6898eb530a9f26f2c
출처 데이터셋
uspto-grants-2011_01
특허 번호
US07875636B2

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