Phenyl isocyanate → HCID 68613235, compound

HRID 2095373Notes

Reaction equation

HRID 2095373 reaction equation
[N+:1]([CH2:4][CH2:5][CH2:6][C:7]([O:9][CH3:10])=[O:8])([O-])=[O:2].[CH3:11][N:12]1[CH2:16][CH2:15][CH2:14][C@H:13]1[CH2:17][O:18][C:19]1[CH:24]=[CH:23][C:22]([C:25]#C)=CN=1.[C:27]1([N:33]=[C:34]=O)C=CC=CC=1.C(N(CC)CC)C>C1C=CC=CC=1.O>[CH3:10][O:9][C:7](=[O:8])[CH2:6][CH2:5][C:4]1[CH:25]=[C:22]([C:23]2[CH:27]=[N:33][CH:34]=[C:19]([O:18][CH2:17][C@@H:13]3[CH2:14][CH2:15][CH2:16][N:12]3[CH3:11])[CH:24]=2)[O:2][N:1]=1

Participants

7

Reactant 4

HCID 7672Phenyl isocyanateHCID 8471TriethylamineHCID 25604Methyl 4-nitrobutyrateHCID 86642676HCID 86642676, compound

Product 1

HCID 68613235HCID 68613235, compoundYield 100.7%

Reagents, catalysts & solvents 2

HCID 241BenzeneSolventHCID 962WaterSolvent

Conditions

Temperature
60 °C

Procedure

To a solution of methyl 4-nitrobutyrate (90 μL, 0.69 mmol, 3.0 equiv.) and 3-[[(1-methyl-2(S)-pyrrolidinyl)methoxy]-5-ethynylpyridine (50 mg, 0.23 mmol) in dry benzene (2.3 mL) were added phenyl isocyanate (80 μL, 0.69 mmol, 3.0 equiv.) and triethylamine (60 μL, 0.46 mmol, 2.0 equiv.). The reaction mixture was stirred at 60° C. for 24 h, then diluted with water and stirred vigorously for 2 h. The mixture was extracted with CH2Cl2, and the organic phase was dried over MgSO4, filtered, and concentrated in vacuo. The residue was purified by CC on SiO2 with CH2Cl2/MeOH 9:1 to give the isoxazole (80 mg, 98%). 1H NMR (CD3OD, 400 MHz) δ 8.58 (s, 1H), 8.39 (s, 1H), 7.57 (s, 1H), 6.51 (s, 1H), 4.09 (dd, 1H, J=9.2, 5.5 Hz), 4.02 (dd, 1H, J=9.2, 5.5 Hz), 3.73 (s, 3H), 3.15 (t, 1H, J=7.2 Hz), 3.07 (t, 2H, J=7.2 Hz), 2.80 (t, 2H, J=7.2 Hz), 2.73 (m, 1H), 2.51 (s, 3H), 2.36 (m, 1H), 2.07 (m, 1H), 1.85 (m, 3H).

Workup

  1. stirringstirred vigorously for 2 h
  2. extractionThe mixture was extracted with CH2Cl2
  3. dry with materialthe organic phase was dried over MgSO4
  4. filtrationfiltered
  5. concentrationconcentrated in vacuo
  6. customThe residue was purified by CC on SiO2 with CH2Cl2/MeOH 9:1

Sources & evidence

ORD record
ord-02a3c6f8ec994fa298f3f1bcc3f88345
Source dataset
uspto-grants-2013_05
Patent number
US08445684B2

Reaction notes

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