1-Butanol → HCID 11855746, compound

HRID 1875413Notes

Reaction equation

HRID 1875413 reaction equation
F[C:2]1[CH:3]=[C:4]([CH:7]=[CH:8][C:9]=1[N:10]1[C:18]2[CH2:17][C:16]([CH3:20])([CH3:19])[CH2:15][C:14](=[O:21])[C:13]=2[CH:12]=[C:11]1[CH3:22])[C:5]#[N:6].[CH2:23]([OH:27])[CH2:24][CH2:25][CH3:26].[H-].[Na+].CN(C=[O:34])C>>[CH2:23]([O:27][C:2]1[CH:3]=[C:4]([CH:7]=[CH:8][C:9]=1[N:10]1[C:18]2[CH2:17][C:16]([CH3:20])([CH3:19])[CH2:15][C:14](=[O:21])[C:13]=2[CH:12]=[C:11]1[CH3:22])[C:5]([NH2:6])=[O:34])[CH2:24][CH2:25][CH3:26]

Participants

5

Reactant 4

HCID 2631-ButanolHCID 6228DimethylformamideHCID 24758Sodium hydrideHCID 11855745HCID 11855745, compound

Product 1

HCID 11855746HCID 11855746, compoundYield 65%

Conditions

Temperature
100 °C

Procedure

3-Fluoro-4-(2,6,6-trimethyl-4-oxo-4,5,6,7-tetrahydro-indol-1-yl)-benzonitrile (148 mg, 0.5 mmol) and 1-butanol (185.3 mg, 2.5 mmol) were dissolved in anhydrous DMF (1.5 mL). To this solution was added NaH (24.0 mg, 1 mmol). After purging the reaction vessel (Personal Chemistry Microwave Vial) with nitrogen, the reaction vessel was sealed and heated to 100° C. for 300 seconds in an Emyrs Optimizer Microwave. After cooling, the reaction mixture was diluted with H2O and extracted into EtOAc (×2). The combined organics were washed with brine (×2), dried over Na2SO4, and concentrated to dryness. The yellow residue (3-Butoxy-4-(2,6,6-trimethyl-4-oxo-4,5,6,7-tetrahydro-indol-1-yl)-benzonitrile) was then dissolved in EtOH (3 mL) and treated with 1 mL of 1 N NaOH (aq) and a catalytic amount of H2O2. Quantitative conversion of the nitrile to the amide occurred after heating this solution at 65° C. for 3 hours. Column chromatography on silica eluting with EtOAc gave the product as a white solid (119.9 mg, 65%). (100% clean by LC/MS, product M+H=369.2).

Workup

  1. customAfter purging the reaction vessel (Personal Chemistry Microwave Vial) with nitrogen
  2. customthe reaction vessel was sealed
  3. temperatureAfter cooling
  4. additionthe reaction mixture was diluted with H2O
  5. extractionextracted into EtOAc (×2)
  6. washThe combined organics were washed with brine (×2)
  7. dry with materialdried over Na2SO4
  8. concentrationconcentrated to dryness
  9. dissolutionThe yellow residue (3-Butoxy-4-(2,6,6-trimethyl-4-oxo-4,5,6,7-tetrahydro-indol-1-yl)-benzonitrile) was then dissolved in EtOH (3 mL)
  10. additiontreated with 1 mL of 1 N NaOH (aq)
  11. temperatureafter heating this solution at 65° C. for 3 hours

Sources & evidence

ORD record
ord-b8b71c51e05347faab2d0b8547221f77
Source dataset
uspto-grants-2012_11
Patent number
US08309548B2

Reaction notes

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