Acetic Acid → HCID 46177418, compound

HRID 2280388Notes

Reaction equation

HRID 2280388 reaction equation
[F:1][C:2]1([F:16])[C:7](O)(O)[CH2:6][CH2:5][N:4](C(=O)C(F)(F)F)[CH2:3]1.[CH2:17]([NH2:24])[C:18]1[CH:23]=[CH:22][CH:21]=[CH:20][CH:19]=1.C([BH3-])#N.[Na+].C(O)(=O)C>C1(C)C=CC=CC=1>[CH2:17]([NH:24][CH:7]1[CH2:6][CH2:5][NH:4][CH2:3][C:2]1([F:1])[F:16])[C:18]1[CH:23]=[CH:22][CH:21]=[CH:20][CH:19]=1

Participants

6

Reactant 4

HCID 176Acetic AcidHCID 7504BenzylamineHCID 5003444Sodium cyanoborohydrideHCID 46177416HCID 46177416, compound

Product 1

HCID 46177418HCID 46177418, compoundYield 73%

Reagents, catalysts & solvents 1

HCID 1140TolueneSolvent

Procedure

In a 100 mL flask, 2.00 g (8.0 mmol) of 3,3-difluoro-4,4-dihydroxy-1-trifluoroacetylpiperidine 13 (J. Org Chem. 2010, 75, 929-932) and 2.15 g (20.0 mmol; 2.5 equiv) of benzylamine were dissolved in 50 mL of toluene. The mixture was heated under reflux with a Dean Stark trap during 15 hours. After cooling to room temperature, the solvent was removed in vacuo. The resulting oil was dissolved in 25 mL of absolute methanol and 0.56 g (8.8 mmol; 1.1 equiv) of sodium cyanoborohydride and 0.48 g (8.0 mmol; 1 equiv) of acetic acid were slowly added at room temperature. The solution was stirred during 4 hours at room temperature. After removing the solvent under vacuum, the crude oil was redissolved in 50 mL of dichloromethane and poured in 50 mL of a saturated aqueous NaHCO3 solution and was subsequently extracted with dichloromethane (3×50 mL). The combined organic layers were washed with brine and dried over MgSO4. Filtration of the solids and evaporation of the solvent resulted in a crude oil which was purified via flash chromatography (EtOAc, Rf=0.03) yielding 1.32 g (5.8 mmol; 73% yield) of benzyl-(3,3-difluoro-piperidin-4-yl)amine 14 as a yellow oil.

Workup

  1. temperatureThe mixture was heated
  2. temperatureunder reflux with a Dean Stark trap during 15 hours
  3. customthe solvent was removed in vacuo
  4. dissolutionThe resulting oil was dissolved in 25 mL of absolute methanol
  5. customAfter removing the solvent under vacuum
  6. dissolutionthe crude oil was redissolved in 50 mL of dichloromethane
  7. additionpoured in 50 mL of a saturated aqueous NaHCO3 solution
  8. extractionwas subsequently extracted with dichloromethane (3×50 mL)
  9. washThe combined organic layers were washed with brine
  10. dry with materialdried over MgSO4
  11. filtrationFiltration of the solids and evaporation of the solvent
  12. customresulted in a crude oil which
  13. customwas purified via flash chromatography (EtOAc, Rf=0.03)

Sources & evidence

ORD record
ord-22b4dfd9781840e5947e91877e1ee7c1
Source dataset
uspto-grants-2015_09
Patent number
US09139523B2

Reaction notes

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