Dimethylformamide → HCID 67441441, compound

HRID 1471604Notes

Reaction equation

HRID 1471604 reaction equation
[OH:1][C:2]1[CH:3]=[C:4]([CH:7]=[CH:8][C:9]=1[O:10][C:11]1[CH:20]=[CH:19][C:14]2[B:15]([OH:18])[O:16][CH2:17][C:13]=2[CH:12]=1)[C:5]#[N:6].[CH:21]1(I)[CH2:25][CH2:24][CH2:23][CH2:22]1.CN(C)C=O.[H-].[Na+]>O>[CH:21]1([O:1][C:2]2[CH:3]=[C:4]([CH:7]=[CH:8][C:9]=2[O:10][C:11]2[CH:20]=[CH:19][C:14]3[B:15]([OH:18])[O:16][CH2:17][C:13]=3[CH:12]=2)[C:5]#[N:6])[CH2:25][CH2:24][CH2:23][CH2:22]1

Participants

6

Reactant 4

HCID 6228DimethylformamideHCID 24758Sodium hydride2×HCID 73784Iodocyclopentane2×HCID 67439736HCID 67439736, compound

Product 1

HCID 67441441HCID 67441441, compoundYield 63.2%

Reagents, catalysts & solvents 1

HCID 962WaterSolvent

Procedure

A solution of 3-hydroxy-4-(1-hydroxy-1,3-dihydrobenzo[c][1,2]oxaborol-5-yloxy)benzonitrile (0.500 g, 1.87 mmol), cyclopentyl iodide (0.65 mL, 5.61 mmol), and N,N-dimethylformamide (30 mL) under a nitrogen balloon was cooled to 0° C. on an ice water bath. Sodium hydride (0.224 g, 5.61 mmol) was added and then the reaction was stirred for 5 minutes on the ice water bath. The reaction was then stirred at room temperature for 2 hours. More cyclopentyl iodide (0.22 mL, 1.87 mmol) was added and the reaction was cooled to 0° C. on an ice water bath. Sodium hydride was added (0.075 g, 1.87 mmol) and the reaction was stirred at 0° C. for 5 minutes. The reaction was then stirred at room temperature for another 2 hours. Water was added to quench excess sodium hydride and the reaction was then neutralized using 1 M HCl. Water was added and the solution was extracted using ethyl acetate. The organic layer was washed with water, brine, dried over anhydrous sodium sulfate, and filtered. The solvent was removed under reduced pressure. The residue was purified by silica gel column using Combiflash to give 3-(cyclopentyloxy)-4-(1-hydroxy-1,3-dihydrobenzo[c][1,2]oxaborol-5-yloxy)benzonitrile (0.396 g, 63% yield). 1H NMR (400 MHz, DMSO-d6) δ ppm 1.25 (m, 2 H), 1.38 (m, 2 H), 1.50 (m, 2 H), 1.73 (m, 2H), 4.86 (m, 2 H), 6.84 (s, 1 H), 6.87 (d, J=8.2 Hz, 1 H), 7.18 (d, J=8.2 Hz, 1 H), 7.40 (d, J=8.4 Hz, 1 H), 7.58 (s, 1 H), 7.64 (d, J=8.0 Hz, 1 H), 9.06 (s, 1 H).

Workup

  1. temperaturethe reaction was cooled to 0° C. on an ice water bath
  2. stirringthe reaction was stirred at 0° C. for 5 minutes
  3. stirringThe reaction was then stirred at room temperature for another 2 hours
  4. customto quench excess sodium hydride
  5. additionWater was added
  6. extractionthe solution was extracted
  7. washThe organic layer was washed with water, brine
  8. dry with materialdried over anhydrous sodium sulfate
  9. filtrationfiltered
  10. customThe solvent was removed under reduced pressure
  11. customThe residue was purified by silica gel column

Sources & evidence

ORD record
ord-f0370620aecc457198398786af785836
Source dataset
uspto-grants-2015_04
Patent number
US09012431B2

Reaction notes

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