Thionyl Chloride → 5-(4,5-Dihydrooxazol-2-yl)-2-isopropoxybenzonitrile

HRID 1053752Notes

Reaction equation

HRID 1053752 reaction equation
[C:1]([C:3]1[CH:4]=[C:5]([CH:12]=[CH:13][C:14]=1[O:15][CH:16]([CH3:18])[CH3:17])[C:6]([NH:8][CH2:9][CH2:10][OH:11])=O)#[N:2].S(Cl)(Cl)=O>C(Cl)Cl>[O:11]1[CH2:10][CH2:9][N:8]=[C:6]1[C:5]1[CH:12]=[CH:13][C:14]([O:15][CH:16]([CH3:18])[CH3:17])=[C:3]([CH:4]=1)[C:1]#[N:2]

Participants

4

Reactant 2

HCID 24386Thionyl ChlorideHCID 583550313-cyano-N-(2-hydroxyethyl)-4-isopropoxybenzamide

Product 1

HCID 583549695-(4,5-Dihydrooxazol-2-yl)-2-isopropoxybenzonitrileYield 61%

Reagents, catalysts & solvents 1

HCID 6344DichloromethaneSolvent

Procedure

3-cyano-N-(2-hydroxyethyl)-4-isopropoxybenzamide was dissolved in DCM (30 mL) and thionyl chloride (1.43 g, 12 mmol) was added at 0° C. The reaction mixture was stirred at room temperature for 1 h and then quenched at 0° C. with water (200 μL) and 6N NaOH solution (1 mL). The mixture was stirred for 30 min. The aqueous layers were extracted with DCM and the combined organic extracts were washed with brine and dried over MgSO4 to afford 570 mg (61% for two steps) of 5-(4,5-dihydrooxazol-2-yl)-2-isopropoxybenzonitrile INT-31. LCMS-ESI (m/z) calculated for C13H14N2O2: 230.3; found 231.0 [M+H]+, tR=2.50 min. 1H NMR (400 MHz, CDCl3) δ 8.17-7.86 (m, 2H), 6.91 (d, J=8.9 Hz, 1H), 4.65 (dt, J=12.2, 6.1 Hz, 1H), 4.37 (dd, J=14.3, 4.9 Hz, 2H), 3.98 (t, J=9.5 Hz, 2H), 1.36 (t, J=5.5 Hz, 6H).

Workup

  1. customquenched at 0° C. with water (200 μL) and 6N NaOH solution (1 mL)
  2. stirringThe mixture was stirred for 30 min
  3. extractionThe aqueous layers were extracted with DCM
  4. washthe combined organic extracts were washed with brine
  5. dry with materialdried over MgSO4

Sources & evidence

ORD record
ord-a389be423db448ed976d1189315ee196
Source dataset
uspto-grants-2016_07
Patent number
US09394264B2

Reaction notes

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