Phenyl isocyanate → HCID 59371644, compound

HRID 2095369Notes

Reaction equation

HRID 2095369 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[CH2:24][CH2:23][CH2:22][C@H:21]1[CH2:25][O:26][C:27]1[CH:28]=[N:29][CH:30]=[C:31]([C:33]#[CH:34])[CH:32]=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[CH2:24][CH2:23][CH2:22][C@H:21]1[CH2:25][O:26][C:27]1[CH:28]=[N:29][CH:30]=[C:31]([C:33]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:34]=2)[CH:32]=1)=[O:19])([CH3:16])([CH3:15])[CH3:14]

Participants

7

Reactant 4

HCID 7672Phenyl isocyanateHCID 8471TriethylamineHCID 37486562-(2-Nitroethoxy)tetrahydropyranHCID 71513570HCID 71513570, compound

Product 1

HCID 59371644HCID 59371644, compoundYield 74%

Reagents, catalysts & solvents 2

HCID 241BenzeneSolventHCID 962WaterSolvent

Procedure

To a solution of 1-nitro-2-(tetrahydro-2H-pyran-2-yloxy)ethane (0.17 mL, 1.12 mmol, 2.0 equiv.) and 3-[[1-(tert-butoxycarbonyl)-2(S)-pyrrolidinyl]methoxy]-5-ethynylpyridine (170 mg, 0.56 mmol) in dry benzene (5.6 mL) were added phenyl isocyanate (122 μL, 1.12 mmol, 2.0 equiv.) and triethylamine (80 μL, 0.57 mmol, 1.0 equiv.). The reaction mixture was stired at 60° C. for 48 h, then diluted with water and stirred vigorously for 2 h. The mixture was extracted with CH2Cl2. The organic phase was dried over MgSO4, filtered, and concentrated in vacuo. The residue was purified by CC on SiO2 with EtOAc/hexane 1:1 to give 3-[[1-(tert-butoxycarbonyl)-2(S)-pyrrolidinyl]methoxy]-5-[3-[(tetrahydro-2H-pyran-2-yloxy)methyl]-5-isoxazolyl]pyridine (190 mg, 74%). The 1H NMR spectrum (CDCl3, 400 MHz) exhibits two sets of signals for two of the heteroaromatic protons: δ 8.53 (br s, 1H), 8.28 (br s, 1H), 7.69 (br s, 1H of the major component), 7.49 (br s, 1H of the minor component), 6.69 (br s, 1H of the major component), 6.65 (br s, 1H of the minor component), 4.75, 4.57 (ABq, 2H, J=12.8 Hz), 4.67 (br s, 1H), 4.23-4.01 (m, 2H), 3.99-3.84 (m, 1H), 3.81 (br t, 1H, J=9.6 Hz), 3.53-3.42 (m, 1H), 3.40-3.20 (m, 2H), 2.03-1.4 (series of overlapping m, 10H), 1.38 (s, 9H).

Workup

  1. extractionThe mixture was extracted with CH2Cl2
  2. dry with materialThe organic phase was dried over MgSO4
  3. filtrationfiltered
  4. concentrationconcentrated in vacuo
  5. customThe residue was purified by CC on SiO2 with EtOAc/hexane 1:1

Sources & evidence

ORD record
ord-76d2148382f045bd9a3d15307f85e2ae
Source dataset
uspto-grants-2013_05
Patent number
US08445684B2

Reaction notes

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