Ethyl Acetate → tert-Butyl 4-(5-aminopyridin-2-yl)piperidine-1-carboxylate

HRID 592347Notes

Reaction equation

HRID 592347 reaction equation
[N+:1]([C:4]1[CH:5]=[CH:6][C:7]([C:10]2[CH2:15][CH2:14][N:13]([C:16]([O:18][C:19]([CH3:22])([CH3:21])[CH3:20])=[O:17])[CH2:12][CH:11]=2)=[N:8][CH:9]=1)([O-])=O.CCOC(C)=O>CN(C=O)C.[Pd]>[NH2:1][C:4]1[CH:5]=[CH:6][C:7]([CH:10]2[CH2:15][CH2:14][N:13]([C:16]([O:18][C:19]([CH3:22])([CH3:21])[CH3:20])=[O:17])[CH2:12][CH2:11]2)=[N:8][CH:9]=1

Participants

5

Reactant 2

HCID 8857Ethyl AcetateHCID 591285695-Nitro-3',6'-dihydro-2'H-[2,4]bipyridinyl-1'-carboxylic acid tert-butyl ester

Product 1

HCID 59128562tert-Butyl 4-(5-aminopyridin-2-yl)piperidine-1-carboxylate

Reagents, catalysts & solvents 2

HCID 23938PalladiumCatalystHCID 6228DimethylformamideSolvent2×

Procedure

A slurry of 10% Pd/C (500 mg) in DMF (5 mL) was added to a solution of tert-butyl 5-nitro-5′,6′-dihydro-[2,4′-bipyridine]-1′(2′H)-carboxylate (I8) (1.40, 4.59 mmol) in DMF (45 mL) and the resulting mixture was stirred under a hydrogen atmosphere for 16 hours at room temperature. EtOAc (100 mL) was added and the resulting suspension was filtered through a Celite pad, washing with EtOAc (150 mL). The volatiles were removed under reduced pressure and the residue was purified by silica gel column chromatography (Biotage Isolera, 40 g Si cartridge, 0-100% EtOAc in petroleum benzine 40-60° C. and then 0-20% MeOH in EtOAc) to give the title compound I9 as a yellow oil (1.18 g, 93%); 1H NMR (400 MHz, CDCl3) δ 8.03 (dd, J=2.4, 1.0 Hz, 1H), 7.00-6.87 (m, 2H), 4.22 (brs, 2H), 3.59 (brs, 2H), 2.85-2.67 (m, 3H), 1.86 (m, 2H), 1.72-1.59 (m, 2H), 1.46 (s, 9H). LCMS-A: rt 4.416 min; m/z 278 [M+H]+.

Workup

  1. filtrationthe resulting suspension was filtered through a Celite pad
  2. washwashing with EtOAc (150 mL)
  3. customThe volatiles were removed under reduced pressure
  4. customthe residue was purified by silica gel column chromatography (Biotage Isolera, 40 g Si cartridge, 0-100% EtOAc in petroleum benzine 40-60° C.

Sources & evidence

ORD record
ord-9773b89b183849f381cc9bc04db2d31d
Source dataset
uspto-grants-2016_01
Patent number
US09238644B2

Reaction notes

Loading…