Phosphorus oxychloride → [2-Methoxy-4-(4,5,6,7-tetrahydro-1,3-benzoxazol-2-yl)phenyl]acetonitrile

HRID 7798Notes

Reaction equation

HRID 7798 reaction equation
[C:1]([CH2:3][C:4]1[CH:19]=[CH:18][C:7]([C:8]([NH:10][CH:11]2[CH2:16][CH2:15][CH2:14][CH2:13][C:12]2=[O:17])=O)=[CH:6][C:5]=1[O:20][CH3:21])#[N:2].O=P(Cl)(Cl)Cl>>[CH3:21][O:20][C:5]1[CH:6]=[C:7]([C:8]2[O:17][C:12]3[CH2:13][CH2:14][CH2:15][CH2:16][C:11]=3[N:10]=2)[CH:18]=[CH:19][C:4]=1[CH2:3][C:1]#[N:2]

Participants

3

Reactant 2

HCID 24813Phosphorus oxychlorideHCID 219909934-(cyanomethyl)-3-methoxy-N-(2-oxocyclohexyl)benzamide

Product 1

HCID 21990992[2-Methoxy-4-(4,5,6,7-tetrahydro-1,3-benzoxazol-2-yl)phenyl]acetonitrile

Procedure

4-(cyanomethyl)-3-methoxy-N-(2-oxocyclohexyl)benzamide (0.8 g, 2.8 mmol) was treated with POCl3 (5 mL) at reflux for 1 h. The resulting mixture was concentrated and dissolved in dichloromethane (50 mL), washed with sat. NaHCO3 (3×15 mL) and sat. brine (3×15 mL), dried (MgSO4), and concentrated in vacuo. The crude residue was chromatographed on silica gel, eluting with 2:1 hexanes:EtOAc to afford the desired compound, [2-methoxy-4-(4,5,6,7-tetrahydro-1,3-benzoxazol-2-yl)phenyl]acetonitrile, the desired compound, as white solid. 1H NMR (CDCl3, 300 MHz) δ 7.58 (dd, 1H), 7.53 (m, 1H), 7.42 (d, 1H), 3.95 (s, 3H), 3.72 (s, 2H), 2.71 (m, 2H), 2.62 (m, 2H), 1.87 (m, 4H). MS (ESI) 269 (M+H)+.

Workup

  1. temperatureat reflux for 1 h
  2. concentrationThe resulting mixture was concentrated
  3. dissolutiondissolved in dichloromethane (50 mL)
  4. washwashed with sat. NaHCO3 (3×15 mL) and sat. brine (3×15 mL)
  5. dry with materialdried (MgSO4)
  6. concentrationconcentrated in vacuo
  7. customThe crude residue was chromatographed on silica gel
  8. washeluting with 2:1 hexanes

Sources & evidence

ORD record
ord-09ec1ce3511b4ca2a186467232961eca
Source dataset
uspto-grants-2006_08
Patent number
US07087601B2

Reaction notes

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