Isopropyl iodide → HCID 69232462, compound

HRID 1181067Notes

Reaction equation

HRID 1181067 reaction equation
[C:1]([O:5][C:6](=[O:39])[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][C:27]([OH:30])=[CH:26][CH:25]=3)[O:21][C:22]=2[CH3:23])=[CH:11][C:10]=1[CH2:31][NH:32][C:33]([O:35][CH:36]([CH3:38])[CH3:37])=[O:34])([CH3:4])([CH3:3])[CH3:2].I[CH:41]([CH3:43])[CH3:42].C([O-])([O-])=O.[K+].[K+]>C(O)C>[C:1]([O:5][C:6](=[O:39])[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:25]=[CH:26][C:27]([O:30][CH:41]([CH3:43])[CH3:42])=[CH:28][CH:29]=3)[O:21][C:22]=2[CH3:23])=[CH:11][C:10]=1[CH2:31][NH:32][C:33]([O:35][CH:36]([CH3:37])[CH3:38])=[O:34])([CH3:4])([CH3:3])[CH3:2]

Participants

5

Reactant 3

HCID 6362Isopropyl iodideHCID 11430Potassium CarbonateHCID 136104127HCID 136104127, compound

Product 1

HCID 69232462HCID 69232462, compoundYield 64.9%

Reagents, catalysts & solvents 1

HCID 702EthanolSolvent

Procedure

A solution of 3-[4-{2-[2-(4-hydroxy-phenyl)-5-methyl-oxazol-4-yl]-ethoxy}-2-(isopropoxycarbonylamino-methyl)-phenyl]-propionic acid tert-butyl ester (300 mg, 0.557 mmol, Example 406) in ethanol (20 mL) was treated with 2-iodopropane (473 mg, 2.78 mmol) and K2CO3 (231 mg, 1.67 mmol) and was heated at reflux overnight. The reaction mixture was cooled and concentrated. The residue was diluted with H2O and ethyl acetate. The layers were separated, and the aqueous layer was extracted with ethyl acetate (2×). The combined organic layers were dried (MgSO4), filtered, and concentrated to yield an oil. Purification using silica gel chromatography (3:1 hexane:ethyl acetate) yielded 3-(2-(isopropoxycarbonylamino-methyl)-4-{2-[2-(4-isopropoxy-phenyl)-5-methyl-oxazol-4-yl]-ethoxy}-phenyl)-propionic acid tert-butyl ester as a yellow oil (210 mg). 1H NMR (300 MHz CDCl3) δ 1.28 (d, 6H), 1.40 (d, 6H), 1.45 (s, 9H), 2.38 (s, 3H), 2.53 (t, 2H), 2.91 (t, 2H), 2.99 (t, 2H), 4.25 (t, 2H), 4.39 (d, 2H), 4.66 (m, 1H), 5.00 (br m, 2H), 6.80 (dd, 1H), 6.87 (d, 1H), 6.95 (d, 2H), 7.13 (d, 1H), 7.95 (d, 2H) MS [ES] 581 (M+H).

Workup

  1. temperaturewas heated
  2. temperatureat reflux overnight
  3. temperatureThe reaction mixture was cooled
  4. concentrationconcentrated
  5. additionThe residue was diluted with H2O and ethyl acetate
  6. customThe layers were separated
  7. extractionthe aqueous layer was extracted with ethyl acetate (2×)
  8. dry with materialThe combined organic layers were dried (MgSO4)
  9. filtrationfiltered
  10. concentrationconcentrated
  11. customto yield an oil
  12. customPurification

Sources & evidence

ORD record
ord-ea27ea2f8a3d4278ba863bdd6dd43359
Source dataset
uspto-grants-2007_10
Patent number
US07282501B2

Reaction notes

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