Phenyl isocyanate → HCID 59371583, compound

HRID 2095371Notes

Reaction equation

HRID 2095371 reaction equation
[N+:1]([CH2:4][CH2:5][CH2:6][C:7]([O:9][CH3:10])=[O:8])([O-])=[O:2].[C:11]([O:15][C:16]([N:18]1[CH2:21][CH2:20][C@H:19]1[CH2:22][O:23][C:24]1[CH:25]=[N:26][CH:27]=[C:28]([C:30]#[CH:31])[CH:29]=1)=[O:17])([CH3:14])([CH3:13])[CH3:12].C1(N=C=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:31]=[C:30]([C:28]2[CH:27]=[N:26][CH:25]=[C:24]([O:23][CH2:22][C@@H:19]3[CH2:20][CH2:21][N:18]3[C:16]([O:15][C:11]([CH3:14])([CH3:13])[CH3:12])=[O:17])[CH:29]=2)[O:2][N:1]=1

Participants

7

Reactant 4

HCID 7672Phenyl isocyanateHCID 8471TriethylamineHCID 25604Methyl 4-nitrobutyrateHCID 56595566HCID 56595566, compound

Product 1

HCID 59371583HCID 59371583, compoundYield 85%

Reagents, catalysts & solvents 2

HCID 241BenzeneSolventHCID 962WaterSolvent

Conditions

Temperature
60 °C

Procedure

To a solution of methyl 4-nitrobutyrate (306 μL, 2.4 mmol) and 3-[[1-(tert-butoxycarbonyl)-2(S)-azetidinyl]methoxy]-5-ethynylpyridine (230 mg, 798 μmol) in dry benzene (8.0 mL) were added phenyl isocyanate (0.26 mL, 2.4 mmol) and triethylamine (0.22 mL, 1.6 mmol). 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 eluting with EtOAc/hexane 1:1 to give the isoxazole (283 mg, 85%). 1H NMR (CD3OD, 400 MHz) δ 8.50 (br s, 2H), 7.62 (s, 1H), 6.53 (s, 1H), 4.55 (br s, 1H), 4.40 (br s, 1H), 4.21 (dd, 1H, J=10.0, 2.4 Hz), 3.91 (t, 2H, J=7.2 Hz), 3.73 (s, 3H), 3.07 (t, 2H, J=7.2 Hz), 2.80 (t, 2H, J=7.2 Hz), 2.38 (m, 2H), 1.42 (s, 9H). 13C NMR (CDCl3, 100 MHz) δ 172.8, 167.1, 163.3, 156.3, 155.4, 139.8, 139.5, 124.3, 117.6, 100.9, 80.0, 69.0, 60.1, 52.0, 47.3, 32.1, 28.8, 21.7, 19.2.

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 eluting with EtOAc/hexane 1:1

Sources & evidence

ORD record
ord-50ad635dff984d50aaf0c8075aea588c
Source dataset
uspto-grants-2013_05
Patent number
US08445684B2

Reaction notes

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