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 1181074Notes

Reaction equation

HRID 1181074 reaction equation
[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]

Participants

5

Reactant 3

HCID 6328Methyl iodide2×HCID 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

Product 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 esterYield 73%

Reagents, catalysts & solvents 1

HCID 6228DimethylformamideSolvent

Procedure

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%).

Workup

  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)

Sources & evidence

ORD record
ord-ba34edbd06884609b7d09cacf9d65d65
Source dataset
uspto-grants-2007_10
Patent number
US07282501B2

Reaction notes

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