Methanol → Methyl 7-(1-(tert-butoxycarbonyl)piperidin-4-yl)-8-oxo-5,6,7,8-tetrahydro-1,7-naphthyridine-2-carboxylate

HRID 531037Notes

Reaction equation

HRID 531037 reaction equation
Cl[C:2]1[C:7]([CH2:8][CH2:9][NH:10][CH:11]2[CH2:16][CH2:15][N:14]([C:17]([O:19][C:20]([CH3:23])([CH3:22])[CH3:21])=[O:18])[CH2:13][CH2:12]2)=[CH:6][CH:5]=[C:4](Cl)[N:3]=1.ClCCl.C(N(CC)CC)C.[C]=O.[CH3:37][OH:38]>C1C=CC(P(C2C=CC=CC=2)[C-]2C=CC=C2)=CC=1.C1C=CC(P(C2C=CC=CC=2)[C-]2C=CC=C2)=CC=1.Cl[Pd]Cl.[Fe+2].O.CN(C=O)C>[C:20]([O:19][C:17]([N:14]1[CH2:15][CH2:16][CH:11]([N:10]2[C:37](=[O:38])[C:2]3[N:3]=[C:4]([C:17]([O:19][CH3:20])=[O:18])[CH:5]=[CH:6][C:7]=3[CH2:8][CH2:9]2)[CH2:12][CH2:13]1)=[O:18])([CH3:23])([CH3:22])[CH3:21]

Participants

9

Reactant 5

HCID 887MethanolHCID 6344DichloromethaneHCID 8471TriethylamineHCID 117992313tert-Butyl 4-((2-(2,6-dichloropyridin-3-yl)ethyl)amino)piperidine-1-carboxylateHCID 178418416HCID 178418416, compound

Product 1

HCID 117992243Methyl 7-(1-(tert-butoxycarbonyl)piperidin-4-yl)-8-oxo-5,6,7,8-tetrahydro-1,7-naphthyridine-2-carboxylate

Reagents, catalysts & solvents 3

HCID 178418228Bis(cyclopenta-1,4-dien-1-yl(diphenyl)phosphane);dichloropalladium;iron(2+)CatalystHCID 962WaterSolventHCID 6228DimethylformamideSolvent

Procedure

A mixture of tert-butyl 4-((2-(2,6-dichloropyridin-3-yl)ethyl)amino)piperidine-1-carboxylate (10.5 g), a dichloromethane adduct of [1,1′-bis(diphenylphosphino)ferrocene]dichloropalladium(II) (2.30 g), triethylamine (11.8 mL), methanol (20 mL), and DMF (60 mL) was stirred at 90° C. for 7 hours in a carbon monooxide (5 atm) atmosphere. Water was added to the reaction mixture, followed by extraction with ethyl acetate. The organic layer was washed with saturated saline and dried over anhydrous magnesium sulfate, and then, the solvent was distilled off under reduced pressure. The residue was purified by silica gel column chromatography (hexane/ethyl acetate) to obtain the title compound (4.01 g).

Workup

  1. extractionfollowed by extraction with ethyl acetate
  2. washThe organic layer was washed with saturated saline
  3. dry with materialdried over anhydrous magnesium sulfate
  4. distillationthe solvent was distilled off under reduced pressure
  5. customThe residue was purified by silica gel column chromatography (hexane/ethyl acetate)

Sources & evidence

ORD record
ord-6380c1cc0c7f434faefcc727afb6ca2d
Source dataset
uspto-grants-2016_05
Patent number
US09353108B2

Reaction notes

Loading…