Isopropanol → HCID 58404446, compound

HRID 1526405Notes

Reaction equation

HRID 1526405 reaction equation
F[C:2]1[CH:9]=[CH:8][C:5]([C:6]#[N:7])=[CH:4][C:3]=1[C:10]([F:13])([F:12])[F:11].[CH:14]([OH:17])([CH3:16])[CH3:15].CC([O-])(C)C.[K+]>C1COCC1>[CH:14]([O:17][C:2]1[CH:9]=[CH:8][C:5]([C:6]#[N:7])=[CH:4][C:3]=1[C:10]([F:13])([F:12])[F:11])([CH3:16])[CH3:15]

Participants

5

Reactant 3

HCID 3776IsopropanolHCID 1442554-Fluoro-3-(trifluoromethyl)benzonitrileHCID 23665647Potassium tert-butoxide

Product 1

HCID 58404446HCID 58404446, compoundYield 98%

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent

Conditions

Temperature
1.5 °C

Procedure

To a solution of 4-fluoro-3-(trifluoromethyl)benzonitrile (154 g, 814 mmol) in THF (1.5 L) was added isopropanol (73.4 g, 1.22 mol). The reaction flask was purged with N2 and cooled in an ice bath (1.5° C. internal temperature). t-BuOK (1.0 M in THF, 847 mL, 847 mmol) was added slowly over 10 minutes via addition funnel (slight exotherm to 31° C. was observed) and let stir at that temperature for 30 min (temp decreased to 18° C. during this time). The ice bath was removed and allowed to stir at room temperature until starting material was consumed as observed by LC/MS (˜20 min). The resulting mixture was quenched with water (500 mL) and the layers were separated. The organic layer was concentrated and the aqueous layer was extracted with MTBE (1 L). The organics were combined and washed with H2O (750 mL) and brine (750 mL). Dried organics over MgSO4, filtered, and concentrated to give 4-isopropoxy-3-(trifluoromethyl)benzonitrile (183 g, 798 mmol, 98% yield) as a yellow solid. Exact mass calculated for C11H10F3N0: 229.1, found: LCMS m/z=230.2, [M+H+]; 1H NMR (400 MHz, CDCl3) δ ppm 1.41 (d, J=6.1 Hz, 6 H), 4.73 (sep, J=6.1 Hz, 1 H), 7.06 (d, J=8.7 Hz, 1 H), 7.75 (dd, J1=8.7, J2=2.1 Hz, 1 H), 7.85 (d, J=1.9 Hz, 1 H).

Workup

  1. customThe reaction flask was purged with N2
  2. customdecreased to 18° C. during this time
  3. customThe ice bath was removed
  4. stirringto stir at room temperature
  5. customwas consumed
  6. customas observed by LC/MS (˜20 min)
  7. customThe resulting mixture was quenched with water (500 mL)
  8. customthe layers were separated
  9. concentrationThe organic layer was concentrated
  10. extractionthe aqueous layer was extracted with MTBE (1 L)
  11. washwashed with H2O (750 mL) and brine (750 mL)
  12. filtrationDried organics over MgSO4, filtered
  13. concentrationconcentrated

Sources & evidence

ORD record
ord-cf089f4577794a688b782230f89e037e
Source dataset
uspto-grants-2015_07
Patent number
US09085581B2

Reaction notes

Loading…