Tert-butyl 2-methylpropanoate → Tert-butyl 2-(9-bromo-1-chlorobenzo[c]-1,6-naphthyridin-6-yl)-2-methylpropanoate

HRID 2193008Notes

Reaction equation

HRID 2193008 reaction equation
[Br:1][C:2]1[CH:17]=[CH:16][C:5]2[C:6](Cl)=[N:7][C:8]3[C:13]([C:4]=2[CH:3]=1)=[C:12]([Cl:14])[N:11]=[CH:10][CH:9]=3.[CH3:18][CH:19]([CH3:27])[C:20]([O:22][C:23]([CH3:26])([CH3:25])[CH3:24])=[O:21].C[Si]([N-][Si](C)(C)C)(C)C.[Na+]>C1(C)C=CC=CC=1>[Br:1][C:2]1[CH:17]=[CH:16][C:5]2[C:6]([C:19]([CH3:27])([CH3:18])[C:20]([O:22][C:23]([CH3:26])([CH3:25])[CH3:24])=[O:21])=[N:7][C:8]3[C:13]([C:4]=2[CH:3]=1)=[C:12]([Cl:14])[N:11]=[CH:10][CH:9]=3

Participants

5

Reactant 3

HCID 519334Tert-butyl 2-methylpropanoateHCID 2724254Sodium bis(trimethylsilyl)amideHCID 593754709-Bromo-1,6-dichlorobenzo[c]-1,6-naphthyridine

Product 1

HCID 59375551Tert-butyl 2-(9-bromo-1-chlorobenzo[c]-1,6-naphthyridin-6-yl)-2-methylpropanoate

Reagents, catalysts & solvents 1

HCID 1140TolueneSolvent

Conditions

Temperature
0 °C

Procedure

To a stirred suspension of 9-bromo-1,6-dichlorobenzo[c]-1,6-naphthyridine (5 g, 15.24 mmol) in Toluene (50 ml) was added tert-butyl 2-methylpropanoate (2.64 g, 18.29 mmol). The reaction mixture was cooled to 0° C. A solution of NaHMDS (1M in THF, 3.35 g, 18.29 mmol) was added dropwise, and the reaction mixture was allowed to warm to room temperature. After 5 hours, the reaction was quenched with aqueous saturated ammonium chloride (50 mL), and extracted with EtOAc (1×100 mL). The organic layer was dried over sodium sulfate, filtered and concentrated. The residue was adsorbed on to silica gel and purified by column chromatography on silica gel, eluting with an EtOAc/Hexanes gradient to afford tert-butyl 2-(9-bromo-1-chlorobenzo[c]-1,6-naphthyridin-6-yl)-2-methylpropanoate. LRMS (ESI) calc'd for (C20H20BrClN2O2) [M+H]+, 437.0; found 437.0.

Workup

  1. temperatureto warm to room temperature
  2. customthe reaction was quenched with aqueous saturated ammonium chloride (50 mL)
  3. extractionextracted with EtOAc (1×100 mL)
  4. dry with materialThe organic layer was dried over sodium sulfate
  5. filtrationfiltered
  6. concentrationconcentrated
  7. custompurified by column chromatography on silica gel
  8. washeluting with an EtOAc/Hexanes gradient

Sources & evidence

ORD record
ord-0386dc7641e64e91bc8c6637af27ef3d
Source dataset
uspto-grants-2012_12
Patent number
US08329722B2

Reaction notes

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