Methyl iodide → 3-(4-[2-(5-Methyl-2-phenyl-oxazol-4-yl)-ethoxy]-2-{[methyl-(2,2,2-trifluoro-acetyl)-amino]-methyl}-phenyl)-propionic acid tert-butyl ester

HRID 1181074노트

반응식

HRID 1181074 반응식
[C:1]([O:5][C:6](=[O:38])[CH2:7][CH2:8][C:9]1[CH:14]=[CH:13][C:12]([O:15][CH2:16][CH2:17][C:18]2[N:19]=[C:20]([C:24]3[CH:29]=[CH:28][CH:27]=[CH:26][CH:25]=3)[O:21][C:22]=2[CH3:23])=[CH:11][C:10]=1[CH2:30][NH:31][C:32](=[O:37])[C:33]([F:36])([F:35])[F:34])([CH3:4])([CH3:3])[CH3:2].[H-].[Na+].I[CH3:42]>CN(C=O)C>[C:1]([O:5][C:6](=[O:38])[CH2:7][CH2:8][C:9]1[CH:14]=[CH:13][C:12]([O:15][CH2:16][CH2:17][C:18]2[N:19]=[C:20]([C:24]3[CH:29]=[CH:28][CH:27]=[CH:26][CH:25]=3)[O:21][C:22]=2[CH3:23])=[CH:11][C:10]=1[CH2:30][N:31]([CH3:42])[C:32](=[O:37])[C:33]([F:34])([F:35])[F:36])([CH3:4])([CH3:2])[CH3:3]

참가 물질

5

반응물 3

HCID 6328Methyl iodide2회HCID 24758Sodium hydrideHCID 589792073-{4-[2-(5-Methyl-2-phenyl-oxazol-4-yl)-ethoxy]-2-[(2,2,2-trifluoro-acetylamino)-methyl]-phenyl}-propionic acid tert-butyl ester

생성물 1

HCID 589793073-(4-[2-(5-Methyl-2-phenyl-oxazol-4-yl)-ethoxy]-2-{[methyl-(2,2,2-trifluoro-acetyl)-amino]-methyl}-phenyl)-propionic acid tert-butyl ester수율 73%

시약·촉매·용매 1

HCID 6228Dimethylformamide용매

실험 절차

A solution of 3-{4-[2-(5-methyl-2-phenyl-oxazol-4-yl)-ethoxy]-2-[(2,2,2-trifluoro-acetylamino)-methyl]-phenyl}-propionic acid tert-butyl ester (151 mg, 0.28 mmol) in dry DMF (10 mL) was cooled in an ice bath and treated with NaH (22 mg, 0.55 mmol, 60% oil dispersion). After the reaction mixture was stirred for 25 min, iodomethane (0.15 mL, 3.0 mmol) was added, and the reaction was allowed to warm to ambient temperature gradually. After 4 h, more iodomethane (0.10 mL, 2 mmol) was added. The mixture was stirred overnight and was partitioned between EtOAc and aqueous LiCl solution. The organic layer was washed with brine, dried (Na2SO4), and concentrated. The residue was purified by silica gel radial chromatography (CH2Cl2/EtOAc 100/0 to 95/5) to give the title compound (111 mg, 73%).

후처리

  1. waitAfter 4 h
  2. stirringThe mixture was stirred overnight
  3. customwas partitioned between EtOAc and aqueous LiCl solution
  4. washThe organic layer was washed with brine
  5. dry with materialdried (Na2SO4)
  6. concentrationconcentrated
  7. customThe residue was purified by silica gel radial chromatography (CH2Cl2/EtOAc 100/0 to 95/5)

출처 및 근거

ORD 기록
ord-ba34edbd06884609b7d09cacf9d65d65
출처 데이터셋
uspto-grants-2007_10
특허 번호
US07282501B2

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