4-Fluorobenzonitrile → tert-Butyl 4-(4-cyanophenoxy)piperidine-1-carboxylate

HRID 459924

Reaction equation

HRID 459924 reaction equation
[C:1]([N:8]1[CH2:13][CH2:12][CH:11]([OH:14])[CH2:10][CH2:9]1)([O:3][C:4]([CH3:7])([CH3:6])[CH3:5])=[O:2].[H-].[Na+].F[C:18]1[CH:25]=[CH:24][C:21]([C:22]#[N:23])=[CH:20][CH:19]=1>CN(C=O)C>[C:4]([O:3][C:1]([N:8]1[CH2:13][CH2:12][CH:11]([O:14][C:18]2[CH:25]=[CH:24][C:21]([C:22]#[N:23])=[CH:20][CH:19]=2)[CH2:10][CH2:9]1)=[O:2])([CH3:7])([CH3:6])[CH3:5]

Participants

5

Reactant 3

HCID 145174-FluorobenzonitrileHCID 24758Sodium hydrideHCID 643502Tert-butyl 4-hydroxypiperidine-1-carboxylate

Product 1

HCID 23019443tert-Butyl 4-(4-cyanophenoxy)piperidine-1-carboxylateYield 52%

Reagents, catalysts & solvents 1

HCID 6228DimethylformamideSolvent3×

Conditions

Temperature
50 °C

Procedure

Add a solution of N-Boc-4-hydroxypiperidine (3.0 g, 14.9 mmol) in DMF (5 mL) to a suspension of sodium hydride (894 mg, 22.4 mmol) in DMF (17 mL). Stir the reaction mixture while heating at 50° C. for 45 min. Then add a solution of 4-fluoro-benzonitrile (2.16 g, 17.9 mmol) in DMF (5 mL). Stir and heat at 50° C. for 2 h. Let cool to room temperature and quench with water (0.5 mL). Evaporate DMF. Redissolved the resulting residue in EtOAc/hexanes (2/1, 20 mL) and wash with water (3×15 mL). Dry the organic layer over magnesium sulfate, filter and concentrate. Purify by chromatography (EtOAc/hexanes 20% and EtOAc/hexanes 10%) to yield the title compound (2.32 g, 52%).

Workup

  1. stirringStir
  2. temperatureheat at 50° C. for 2 h
  3. temperatureLet cool to room temperature
  4. customquench with water (0.5 mL)
  5. dissolutionRedissolved the resulting residue in EtOAc/hexanes (2/1, 20 mL)
  6. washwash with water (3×15 mL)
  7. dry with materialDry the organic layer over magnesium sulfate
  8. filtrationfilter
  9. concentrationconcentrate
  10. customPurify by chromatography (EtOAc/hexanes 20% and EtOAc/hexanes 10%)

Sources & evidence

ORD record
ord-c09ff511267348f291cb8b9649589e3c
Source dataset
uspto-grants-2007_03
Patent number
US07196100B2

Linked notes

Loading…