Iodoethane → 3-(4-[2-(2-Biphenyl-4-yl-5-methyl-oxazol-4-yl)-ethoxy]-2-[(ethyl-isopropoxycarbonyl-amino)-methyl]-phenyl)-propionic acid

HRID 1181079Notes

Reaction equation

HRID 1181079 reaction equation
C[O:2][C:3](=[O:41])[CH2:4][CH2:5][C:6]1[CH:11]=[CH:10][C:9]([O:12][CH2:13][CH2:14][C:15]2[N:16]=[C:17]([C:21]3[CH:26]=[CH:25][C:24]([C:27]4[CH:32]=[CH:31][CH:30]=[CH:29][CH:28]=4)=[CH:23][CH:22]=3)[O:18][C:19]=2[CH3:20])=[CH:8][C:7]=1[CH2:33][NH:34][C:35]([O:37][CH:38]([CH3:40])[CH3:39])=[O:36].C[Si]([N-][Si](C)(C)C)(C)C.[Na+].[CH2:52](I)[CH3:53]>CN(C=O)C.CCOC(C)=O>[C:24]1([C:27]2[CH:28]=[CH:29][CH:30]=[CH:31][CH:32]=2)[CH:23]=[CH:22][C:21]([C:17]2[O:18][C:19]([CH3:20])=[C:15]([CH2:14][CH2:13][O:12][C:9]3[CH:10]=[CH:11][C:6]([CH2:5][CH2:4][C:3]([OH:2])=[O:41])=[C:7]([CH2:33][N:34]([CH2:52][CH3:53])[C:35]([O:37][CH:38]([CH3:40])[CH3:39])=[O:36])[CH:8]=3)[N:16]=2)=[CH:26][CH:25]=1

Participants

6

Reactant 3

HCID 6340IodoethaneHCID 2724254Sodium bis(trimethylsilyl)amideHCID 589792543-[4-[2-(2-Biphenyl-4-yl-5-methyl-oxazol-4-yl)-ethoxy]-2-(isopropoxycarbonylamino-methyl)-phenyl]-propionic acid methyl ester

Product 1

HCID 179843883-(4-[2-(2-Biphenyl-4-yl-5-methyl-oxazol-4-yl)-ethoxy]-2-[(ethyl-isopropoxycarbonyl-amino)-methyl]-phenyl)-propionic acidYield 97.8%

Reagents, catalysts & solvents 2

HCID 6228DimethylformamideSolventHCID 8857Ethyl AcetateSolvent

Procedure

A solution of 3-[4-[2-(2-biphenyl-4-yl-5-methyl-oxazol-4-yl)-ethoxy]-2-(isopropoxycarbonylamino-methyl)-phenyl]-propionic acid methyl ester (200 mg, 0.36 mmol) in DMF (15 mL) was treated with sodium bis(trimethylsilyl)amide (132 mg, 0.719 mmol). Ethyl iodide (112 mg, 0.719 mmol) was added, and the reaction mixture was stirred overnight at room temperature under N2. The mixture was diluted with EtOAc (100 mL) and washed with brine (100 mL), then water (100 mL). The organic layer was dried (MgSO4) and concentrated to the penultimate ester as white solid (179 mg). The material was dissolved in EtOH (20 mL), treated with 5N NaOH (20 mL), and stirred at room temperature overnight. The mixture was acidified with 1N HCl (10 mL) and extracted with EtOAc (50 mL). The organics were dried (MgSO4) and concentrated to give a white solid (201 mg). MS [EI+] m/z 571 (M+H)+. Anal. Calculated for C34H38N2O6: C, 71.6; H, 6.7; N, 4.9. Found: C, 70.8; H, 6.8; N, 5.0.

Workup

  1. washwashed with brine (100 mL)
  2. dry with materialThe organic layer was dried (MgSO4)
  3. concentrationconcentrated to the penultimate ester as white solid (179 mg)
  4. dissolutionThe material was dissolved in EtOH (20 mL)
  5. additiontreated with 5N NaOH (20 mL)
  6. stirringstirred at room temperature overnight
  7. extractionextracted with EtOAc (50 mL)
  8. dry with materialThe organics were dried (MgSO4)
  9. concentrationconcentrated

Sources & evidence

ORD record
ord-72b697c3f79b4c5eb6d9fe20da6d38e4
Source dataset
uspto-grants-2007_10
Patent number
US07282501B2

Reaction notes

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