Sodium borohydride → 1-[5-(1-Aminomethyl-4,4-difluoro-cyclohexyl)-pyridin-2-yl]-ethanol

HRID 512158Notes

Reaction equation

HRID 512158 reaction equation
[C:1]([C:4]1[N:9]=[CH:8][C:7]([C:10]2([C:18]#[N:19])[CH2:15][CH2:14][C:13]([F:17])([F:16])[CH2:12][CH2:11]2)=[CH:6][CH:5]=1)(=[O:3])[CH3:2].[BH4-].[Na+]>C1COCC1>[NH2:19][CH2:18][C:10]1([C:7]2[CH:6]=[CH:5][C:4]([CH:1]([OH:3])[CH3:2])=[N:9][CH:8]=2)[CH2:15][CH2:14][C:13]([F:17])([F:16])[CH2:12][CH2:11]1

Participants

4

Reactant 2

HCID 4311764Sodium borohydrideHCID 867161801-(6-Acetyl-pyridin-3-yl)-4,4-difluoro-cyclohexanecarbonitrile

Product 1

HCID 867161811-[5-(1-Aminomethyl-4,4-difluoro-cyclohexyl)-pyridin-2-yl]-ethanolYield 78.9%

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent

Procedure

To a solution of 1-(6-acetyl-pyridin-3-yl)-4,4-difluoro-cyclohexanecarbonitrile (80 mg, 0.30 mmol) in THF (4.0 mL) at room temperature was added sodium borohydride (23 mg, 0.60 mmol) and the reaction was stirred at room temperature for 2.5 hours. The reaction was quenched with methanol and the volatiles were then removed under reduced pressure. The residue was taken up in AcOEt (about 10 mL) and washed with saturated aqueous sodium bicarbonate (about 10 mL). The layers were separated and the aqueous layer was extracted again with AcOEt (2×5 mL). The combined organic layers were washed with brine, dried over sodium sulfate, filtered and concentrated under reduced pressure. The residue was then dissolved in a 7 N ammonia solution in methanol (6.7 mL) and treated with the tip of a spatula of Raney-nickel. The flask was purged three times then left to stir under one atmosphere of hydrogen for 15 hours. The catalyst was removed by filtration through celite and washed with methanol. The solvent was then removed under reduced pressure to afford 1-[5-(1-aminomethyl-4,4-difluoro-cyclohexyl)-pyridin-2-yl]-ethanol as a white solid (64 mg, 78%). LC-MS (m/z) 271.1 (MH+); tR=0.55.

Workup

  1. customThe reaction was quenched with methanol
  2. customthe volatiles were then removed under reduced pressure
  3. washwashed with saturated aqueous sodium bicarbonate (about 10 mL)
  4. customThe layers were separated
  5. extractionthe aqueous layer was extracted again with AcOEt (2×5 mL)
  6. washThe combined organic layers were washed with brine
  7. dry with materialdried over sodium sulfate
  8. filtrationfiltered
  9. concentrationconcentrated under reduced pressure
  10. dissolutionThe residue was then dissolved in a 7 N ammonia solution in methanol (6.7 mL)
  11. additiontreated with the tip of a spatula of Raney-nickel
  12. customThe flask was purged three times
  13. waitthen left
  14. stirringto stir under one atmosphere of hydrogen for 15 hours
  15. customThe catalyst was removed by filtration through celite
  16. washwashed with methanol
  17. customThe solvent was then removed under reduced pressure

Sources & evidence

ORD record
ord-d16f52c0ef53401a926d8bedaa7a8a29
Source dataset
uspto-grants-2015_08
Patent number
US09102591B2

Reaction notes

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