Salicylaldehyde → Tert-butyl 4-(2-formylphenoxy)piperidine-1-carboxylate

HRID 85111Notes

Reaction equation

HRID 85111 reaction equation
[OH:1][C:2]1[CH:9]=[CH:8][CH:7]=[CH:6][C:3]=1[CH:4]=[O:5].CS(O[CH:15]1[CH2:20][CH2:19][N:18]([C:21]([O:23][C:24]([CH3:27])([CH3:26])[CH3:25])=[O:22])[CH2:17][CH2:16]1)(=O)=O.C([O-])([O-])=O.[K+].[K+]>[I-].C([N+](CCCC)(CCCC)CCCC)CCC.CN(C=O)C>[CH:4]([C:3]1[CH:6]=[CH:7][CH:8]=[CH:9][C:2]=1[O:1][CH:15]1[CH2:20][CH2:19][N:18]([C:21]([O:23][C:24]([CH3:27])([CH3:26])[CH3:25])=[O:22])[CH2:17][CH2:16]1)=[O:5]

Participants

6

Reactant 3

HCID 6998SalicylaldehydeHCID 11430Potassium CarbonateHCID 41848691-(tert-Butoxycarbonyl)-4-(methanesulfonyloxy)piperidine

Product 1

HCID 58279027Tert-butyl 4-(2-formylphenoxy)piperidine-1-carboxylateYield 27.4%

Reagents, catalysts & solvents 2

HCID 67553Tetrabutylammonium IodideCatalystHCID 6228DimethylformamideSolvent

Conditions

Temperature
75 °C

Procedure

A mixture containing 2-hydroxybenzaldehyde (25; 4.2 g, 34.5 mmol), tert-butyl 4-(methylsulfonyloxy)piperidine-1-carboxylate (24; 15.0 g, ˜41 mmol), K2CO3 (7.15 g, 51.7 mmol) and tetrabutyl ammonium iodide (500 mg, cat) in DMF (100 mL) was stirred at 70-80° C. for 18 h. The solvent DMF was removed by concentration under reduced pressure. The resulting residue was diluted with EtOAc (100 mL) and washed with water (50 mL). The organic layer was dried (MgSO4) and concentrated under reduced pressure. The resulting residue was purified by chromatography (pentane/EtOAc=1:10) to give tert-butyl 4-(2-formylphenoxy)piperidine-1-carboxylate 26 as a yellow oil (2.89 g, 27%).

Workup

  1. customThe solvent DMF was removed by concentration under reduced pressure
  2. additionThe resulting residue was diluted with EtOAc (100 mL)
  3. washwashed with water (50 mL)
  4. dry with materialThe organic layer was dried (MgSO4)
  5. concentrationconcentrated under reduced pressure
  6. customThe resulting residue was purified by chromatography (pentane/EtOAc=1:10)

Sources & evidence

ORD record
ord-e18c9c4944644f6ab9b899331c62e91f
Source dataset
uspto-grants-2014_09
Patent number
US08846947B2

Reaction notes

Loading…