Phenyl isocyanate → HCID 59371321, compound

HRID 2095367Notes

Reaction equation

HRID 2095367 reaction equation
[N+:1]([CH2:4][CH2:5][O:6][CH:7]1[CH2:12][CH2:11][CH2:10][CH2:9][O:8]1)([O-:3])=O.[C:13]([O:17][C:18]([N:20]1[CH2:23][CH2:22][C@H:21]1[CH2:24][O:25][C:26]1[CH:27]=[N:28][CH:29]=[C:30]([C:32]#[CH:33])[CH:31]=1)=[O:19])([CH3:16])([CH3:15])[CH3:14].C1(N=C=O)C=CC=CC=1.C(N(CC)CC)C>C1C=CC=CC=1.O>[C:13]([O:17][C:18]([N:20]1[CH2:23][CH2:22][C@H:21]1[CH2:24][O:25][C:26]1[CH:27]=[N:28][CH:29]=[C:30]([C:32]2[O:3][N:1]=[C:4]([CH2:5][O:6][CH:7]3[CH2:12][CH2:11][CH2:10][CH2:9][O:8]3)[CH:33]=2)[CH:31]=1)=[O:19])([CH3:16])([CH3:15])[CH3:14]

Participants

7

Reactant 4

HCID 7672Phenyl isocyanateHCID 8471TriethylamineHCID 37486562-(2-Nitroethoxy)tetrahydropyranHCID 56595566HCID 56595566, compound

Product 1

HCID 59371321HCID 59371321, compoundYield 82.7%

Reagents, catalysts & solvents 2

HCID 241BenzeneSolventHCID 962WaterSolvent

Conditions

Temperature
60 °C

Procedure

To a solution of 1-nitro-2-(tetrahydro-2H-pyran-2-yloxy)ethane (Basra, S. K.; Drew, M. G. B.; Mann, J.; Kane, P. D. J. Chem. Soc., Perkin Trans. 1, 2000, 3592-3598) (0.53 mL, 3.4 mmol, 3.0 equiv.) and 3-[[1-(tert-butoxycarbonyl)-2(S)-azetidinyl]methoxy]-5-ethynylpyridine (330 mg, 1.14 mmol) in dry benzene (11 mL) were added phenyl isocyanate (0.37 mL, 3.4 mmol, 3.0 equiv.) and triethylamine (0.70 mL, 5.0 mmol, 4.4 equiv.). The reaction mixture was stirred at 60° C. for 24 h, then diluted with water, stirred vigorously for 2 h, and extracted with CH2Cl2. The combined organic phases were dried over MgSO4, filtered, and concentrated in vacuo. The residue was purified by CC on SiO2 with EtOAc/hexane 1:1 to give the isoxazole (420 mg, 82%). 1H NMR (CDCl3, 400 MHz) δ 8.64 (br s, 1H), 8.41 (br s, 1H), 7.64 (s, 1H), 6.71 (s, 1H), 4.86 (d, 1H, J=12.0 Hz), 4.77 (t, 1H, J=4.0 Hz), 4.68 (d, 1H, J=12.0 Hz), 4.55 (m, 1H), 4.41 (m, 1H), 4.21 (dd, 1H, J=8.0, 4.0 Hz), 3.91 (t, 3H, J=8.0 Hz), 3.59 (m, 1H), 2.38 (m, 2H), 1.78 (m, 2H), 1.58 (m, 4H), 1.42 (s, 9H).

Workup

  1. stirringstirred vigorously for 2 h
  2. extractionextracted with CH2Cl2
  3. dry with materialThe combined organic phases were dried over MgSO4
  4. filtrationfiltered
  5. concentrationconcentrated in vacuo
  6. customThe residue was purified by CC on SiO2 with EtOAc/hexane 1:1

Sources & evidence

ORD record
ord-a41390eaa42c45d3b6a10b315874f468
Source dataset
uspto-grants-2013_05
Patent number
US08445684B2

Reaction notes

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