Oxazole → Methyl 3-[(dipropylamino)carbonyl]-5-(1,3-oxazol-2-yl)benzoate

HRID 348864Notes

Reaction equation

HRID 348864 reaction equation
[O:1]1[CH:5]=[CH:4][N:3]=[CH:2]1.C([Li])CCC.[CH2:11]([N:14]([CH2:28][CH2:29][CH3:30])[C:15]([C:17]1[CH:18]=[C:19]([CH:24]=[C:25](I)[CH:26]=1)[C:20]([O:22][CH3:23])=[O:21])=[O:16])[CH2:12][CH3:13]>O1CCCC1.C(OCC)(=O)C.[Cl-].[Zn+2].[Cl-].C1(P(C2C=CC=CC=2)C2C=CC=CC=2)C=CC=CC=1.C1(P(C2C=CC=CC=2)C2C=CC=CC=2)C=CC=CC=1.C1(P(C2C=CC=CC=2)C2C=CC=CC=2)C=CC=CC=1.C1(P(C2C=CC=CC=2)C2C=CC=CC=2)C=CC=CC=1.[Pd]>[CH2:28]([N:14]([CH2:11][CH2:12][CH3:13])[C:15]([C:17]1[CH:18]=[C:19]([CH:24]=[C:25]([C:2]2[O:1][CH:5]=[CH:4][N:3]=2)[CH:26]=1)[C:20]([O:22][CH3:23])=[O:21])=[O:16])[CH2:29][CH3:30]

Participants

8

Reactant 3

HCID 9255OxazoleHCID 21086179Methyl 3-[(dipropylamino)carbonyl]-5-iodobenzoateHCID 178418339Butyllithium

Product 1

HCID 21939658Methyl 3-[(dipropylamino)carbonyl]-5-(1,3-oxazol-2-yl)benzoate

Reagents, catalysts & solvents 4

HCID 3007855ZincchlorideCatalystHCID 11979704Tetrakis(triphenylphosphine)palladiumCatalystHCID 8028TetrahydrofuranSolvent2×HCID 8857Ethyl AcetateSolvent

Conditions

Temperature
0 °C

Procedure

3-[(Dipropylamino)carbonyl]-5-iodobenzoic acid (12 g, 32 mmol) is dissolved in 20% methanol/benzene (480 mL), and 2M trimethylsilyldiazomethane in hexane (19 mL, 38 mmol) is added slowly. Upon completion of the addition, the solution is concentrated under reduced pressure to give methyl 3-[(dipropylamino)carbonyl]-5-iodobenzoate for use without further purification in the following reaction. To a −70° C. stirred solution of oxazole (120 mg, 1.7 mmol) in tetrahydrofuran (4 mL) is added n-butyllithium (1.6 M in hexanes, 1.2 mL, 1.9 mmol). After 30 min, zinc chloride (1 M in diethyl ether, 5.2 mL, 5.2 mmol) is added and the reaction mixture is warmed to 0° C. for 1 h. To this mixture is added a solution of methyl 3-[(dipropylamino)carbonyl]-5-iodobenzoate (643 mg, 1.6 mmol) in anhydrous tetrahydrofuran (3 mL) followed by palladium(0) tetrakis(triphenylphosphine) (80 mg, 0.07 mmol). The reaction mixture is heated at reflux for 3 h. The reaction mixture is cooled, diluted with ethyl acetate, filtered, washed with saturated sodium bicarbonate, water, and brine, dried (sodium sulfate), filtered, and concentrated under reduced pressure. Purification by flash column chromatography (silica gel, 60% ethyl acetate/hexane) provides the title compound in pure form. 1H NMR (400 MHz, CDCl3) δ 8.77 (s, 1H), 8.27 (s, 1H), 8.14 (s, 1H), 7.80 (s, 1H) 7.32 (s, 1H), 3.52 (t, 2H), 3.22 (t, 2H), 1.75 (m, 2H), 1.30 (m, 2H), 0.97 (t, 3H), 0.79 (t, 3H).

Workup

  1. customwithout further purification
  2. customin the following reaction
  3. temperatureThe reaction mixture is heated
  4. temperatureat reflux for 3 h
  5. temperatureThe reaction mixture is cooled
  6. filtrationfiltered
  7. washwashed with saturated sodium bicarbonate, water, and brine
  8. dry with materialdried (sodium sulfate)
  9. filtrationfiltered
  10. concentrationconcentrated under reduced pressure
  11. customPurification by flash column chromatography (silica gel, 60% ethyl acetate/hexane)

Sources & evidence

ORD record
ord-f65799a8e74d4046bf2502efab824c4c
Source dataset
uspto-grants-2007_02
Patent number
US07176242B2

Reaction notes

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