Isobutanol → HCID 66746696, compound

HRID 1467050Notes

Reaction equation

HRID 1467050 reaction equation
[H-].[Na+].[CH3:3][CH:4]([CH3:7])[CH2:5][OH:6].[NH2:8][C:9]1[CH:16]=[CH:15][CH:14]=[C:13](F)[C:10]=1[C:11]#[N:12]>C1COCC1>[NH2:8][C:9]1[CH:16]=[CH:15][CH:14]=[C:13]([O:6][CH2:5][CH:4]([CH3:7])[CH3:3])[C:10]=1[C:11]#[N:12]

Participants

5

Reactant 3

HCID 6560IsobutanolHCID 24758Sodium hydrideHCID 5226592-Amino-6-fluorobenzonitrile

Product 1

HCID 66746696HCID 66746696, compound

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent

Conditions

Temperature
35 °C

Procedure

Sodium hydride (60% suspension in oil, 25.0 g, 0.625 mol) was suspended in anhydrous THF (1000 mL) under nitrogen and heated to an internal temperature of 40° C. to 45° C. 2-methylpropan-1-ol (61.2 mL, 0.661 mol) was then added slowly and portionwise. The mixture was heated at 40° C. to 45° C. for 1 hour, then cooled to 35° C. 2-amino-6-fluorobenzonitrile (50.0 g, 0.367 mol) was added and refluxed for 21 hours. The mixture was cooled to r.t., then ice (250 g), ice water (750 mL), and hexanes (1000 mL) was added. Insoluble solids were filtered out and the organic layer was separated. The aqueous layer was extracted once more with a mixture of diethyl ether (250 mL) and hexanes (250 mL). The combined organic layer was washed twice with a solution of citric acid (53 g) in water (500 mL), then washed with 80% brine (300 mL), then dried with magnesium sulfate, filtered and concentrated under reduced pressure. The residue was dissolved in methanol (500 mL), and the immiscible oil carried through from the sodium hydride suspension was separated off in a separatory funnel. The solvent was evaporated under vacuum, and the residue was washed with hexanes (250 mL), after which the product 2-amino-6-isobutoxybenzonitrile was obtained as a viscous oil (46 grams, yield: 66%). 1H NMR (400 MHz, DMSO-d6) δ 7.16 (t, J=8.0 Hz, 1H), 6.33 (d, J=8.0 Hz, 1H), 6.17 (d, J=8.0 Hz, 1H), 5.97 (s, 2H), 3.75 (d, J=7.2 Hz, 2H), 2.00 (m, 1H), 0.97 (d, J=6.8 Hz, 6H) ppm. MS 191 (MH+).

Workup

  1. temperatureheated to an internal temperature of 40° C. to 45° C
  2. temperatureThe mixture was heated at 40° C. to 45° C. for 1 hour
  3. temperaturerefluxed for 21 hours
  4. temperatureThe mixture was cooled to r.t.
  5. filtrationInsoluble solids were filtered out
  6. customthe organic layer was separated
  7. extractionThe aqueous layer was extracted once more with a mixture of diethyl ether (250 mL) and hexanes (250 mL)
  8. washThe combined organic layer was washed twice with a solution of citric acid (53 g) in water (500 mL)
  9. washwashed with 80% brine (300 mL)
  10. dry with materialdried with magnesium sulfate
  11. filtrationfiltered
  12. concentrationconcentrated under reduced pressure
  13. dissolutionThe residue was dissolved in methanol (500 mL)
  14. customwas separated off in a separatory funnel
  15. customThe solvent was evaporated under vacuum
  16. washthe residue was washed with hexanes (250 mL)

Sources & evidence

ORD record
ord-da17c78f838043b08d33545da52b6021
Source dataset
uspto-grants-2015_04
Patent number
US09000054B2

Reaction notes

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