Sodium hydride → HCID 66746619, compound

HRID 2410168Notes

Reaction equation

HRID 2410168 reaction equation
[OH:1][CH2:2][C:3]([CH3:11])([CH3:10])[C:4]([NH:6][CH:7]([CH3:9])[CH3:8])=[O:5].[H-].[Na+].[NH2:14][C:15]1[CH:22]=[CH:21][CH:20]=[C:19](F)[C:16]=1[C:17]#[N:18]>C1COCC1>[NH2:14][C:15]1[C:16]([C:17]#[N:18])=[C:19]([CH:20]=[CH:21][CH:22]=1)[O:1][CH2:2][C:3]([CH3:10])([CH3:11])[C:4]([NH:6][CH:7]([CH3:8])[CH3:9])=[O:5]

Participants

5

Reactant 3

HCID 24758Sodium hydrideHCID 5226592-Amino-6-fluorobenzonitrileHCID 86662304HCID 86662304, compound

Product 1

HCID 66746619HCID 66746619, compoundYield 50%

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent

Conditions

Temperature
0 °C

Procedure

To a solution of 3-hydroxy-N-isopropyl-2,2-dimethylpropanamide (Example 1c, 5.12 g, 32.15 mmol) in dry THF (100 mL) was added portion-wise NaH (60% in mineral oil, 1.41 g, 35.37 mmol) at 0° C. under nitrogen. The reaction mixture was stirred at 0° C. for about 30 minutes until bubbling ceased. 2-Amino-6-fluorobenzonitrile (4.38 g, 32.15 mmol) was added and the solution stirred at 80° C. overnight. The reaction mixture was quenched slowly with water at 0° C., and concentrated under reduced pressure. The residue was taken up in EtOAc and washed consecutively with brine and water, dried over Na2SO4 and concentrated. The residue was purified by re-crystallization from EtOAc/hexane to give the title compound as a white crystalline solid (4.4 g, 50%). 1H NMR (400 MHz, CDCl3) δ 1.18 (d, J=6.8 Hz, 6H), 1.32 (s, 6H), 3.94 (s, 2H), 4.04-4.12 (m, 1H), 4.43 (s, 2H), 5.98 (d, J=6.8 Hz, 1H), 6.21 (d, J=8.0 Hz, 1H), 6.32 (d, J=8.0 Hz, 1H), 7.21 (t, J=8.0 Hz, 1H). MS 276 (MH+).

Workup

  1. customuntil bubbling
  2. stirringthe solution stirred at 80° C. overnight
  3. customThe reaction mixture was quenched slowly with water at 0° C.
  4. concentrationconcentrated under reduced pressure
  5. washwashed consecutively with brine and water
  6. dry with materialdried over Na2SO4
  7. concentrationconcentrated
  8. customThe residue was purified by re-crystallization from EtOAc/hexane

Sources & evidence

ORD record
ord-b6a88aa0638445a0a94489d98be60397
Source dataset
uspto-grants-2014_08
Patent number
US08815956B2

Reaction notes

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