Acetic Acid → 2-(1-(3-Fluoro-4-nitrobenzyl)piperidin-4-yl)propan-2-ol

HRID 518755Notes

Reaction equation

HRID 518755 reaction equation
[F:1][C:2]1[CH:3]=[C:4]([CH:7]=[CH:8][C:9]=1[N+:10]([O-:12])=[O:11])[CH:5]=O.[NH:13]1[CH2:18][CH2:17][CH:16]([C:19]([OH:22])([CH3:21])[CH3:20])[CH2:15][CH2:14]1.CC(O)=O.C(O[BH-](OC(=O)C)OC(=O)C)(=O)C.[Na+]>C(Cl)Cl>[F:1][C:2]1[CH:3]=[C:4]([CH:7]=[CH:8][C:9]=1[N+:10]([O-:12])=[O:11])[CH2:5][N:13]1[CH2:18][CH2:17][CH:16]([C:19]([OH:22])([CH3:21])[CH3:20])[CH2:15][CH2:14]1

Participants

6

Reactant 4

HCID 176Acetic AcidHCID 38081203-Fluoro-4-nitrobenzaldehydeHCID 5049666Sodium triacetoxyborohydrideHCID 52003212-(4-Piperidyl)-2-propanol

Product 1

HCID 601958222-(1-(3-Fluoro-4-nitrobenzyl)piperidin-4-yl)propan-2-olYield 86%

Reagents, catalysts & solvents 1

HCID 6344DichloromethaneSolvent

Procedure

To a solution of 3-fluoro-4-nitrobenzaldehyde (0.5 g, 2.96 mmol) and 2-(piperidin-4-yl)propan-2-ol (0.466 g, 3.25 mmol) in DCM (25 mL) was added AcOH (0.017 mL, 0.296 mmol) and sodium triacetoxyborohydride (0.689 g, 3.25 mmol), and the reaction was stirred at RT for 1 hour. After 1 hour, the reaction was quenched by the addition of 1 N aqueous NaOH (15 mL), and the layers were separated. The aqueous layer was extracted with DCM, and the combined organic layers were washed with brine, dried over anhydrous magnesium sulfate, filtered, and concentrated. The residual product was adsorbed onto a plug of silica gel, and purified by column chromatography, eluting with 0-100% EtOAc in DCM, to provide 2-(1-(3-fluoro-4-nitrobenzyl)piperidin-4-yl)propan-2-ol as a yellow oil (0.75 g, 86% yield).

Workup

  1. waitAfter 1 hour
  2. customthe reaction was quenched by the addition of 1 N aqueous NaOH (15 mL)
  3. customthe layers were separated
  4. extractionThe aqueous layer was extracted with DCM
  5. washthe combined organic layers were washed with brine
  6. dry with materialdried over anhydrous magnesium sulfate
  7. filtrationfiltered
  8. concentrationconcentrated
  9. custompurified by column chromatography
  10. washeluting with 0-100% EtOAc in DCM

Sources & evidence

ORD record
ord-f98dc9b6640e48488152742be7095de6
Source dataset
uspto-grants-2015_08
Patent number
US09115127B2

Reaction notes

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