N-Methoxy-N-methylbenzamide → 6-Benzoyl-3,3-dimethyl-2,3-dihydro-pyrrolo[3,2-b]pyridine-1-carboxylic acid tert-butyl ester

HRID 1475495Notes

Reaction equation

HRID 1475495 reaction equation
C([Li])CCC.[C:6]([O:10][C:11]([N:13]1[C:21]2[C:16](=[N:17][CH:18]=[C:19](Br)[CH:20]=2)[C:15]([CH3:24])([CH3:23])[CH2:14]1)=[O:12])([CH3:9])([CH3:8])[CH3:7].CON(C)[C:28](=[O:35])[C:29]1[CH:34]=[CH:33][CH:32]=[CH:31][CH:30]=1>C(OCC)C>[C:6]([O:10][C:11]([N:13]1[C:21]2[C:16](=[N:17][CH:18]=[C:19]([C:28](=[O:35])[C:29]3[CH:34]=[CH:33][CH:32]=[CH:31][CH:30]=3)[CH:20]=2)[C:15]([CH3:24])([CH3:23])[CH2:14]1)=[O:12])([CH3:9])([CH3:8])[CH3:7]

Participants

5

Reactant 3

HCID 569575N-Methoxy-N-methylbenzamideHCID 70980192HCID 70980192, compoundHCID 178418339Butyllithium

Product 1

HCID 709810756-Benzoyl-3,3-dimethyl-2,3-dihydro-pyrrolo[3,2-b]pyridine-1-carboxylic acid tert-butyl esterYield 68.1%

Reagents, catalysts & solvents 1

HCID 3283Diethyl EtherSolvent2×

Procedure

n-Butyl lithium (5.0 mL of a 2.5 M solution in hexanes, 12 mmol) was added dropwise to a solution of 6-bromo-3,3-dimethyl-2,3-dihydro-pyrrolo[3,2-b]pyridine-1-carboxylic acid tert-butyl ester (3.27 g, 10.0 mmol) in diethyl ether (20 mL) at −78° C. The resulting orange slurry was stirred 30 minutes at this temperature, then a solution of N-methoxy-N-methyl-benzamide (2.3 mL, 15.0 mmol) in diethyl ether (10 mL) was added dropwise. The reaction was allowed to warm to room temperature and stirred 1 h further, then quenched with saturated aqueous ammonium chloride and the two layers were separated. The aqueous fraction was further extracted with EtOAc (2×20 mL). The combined organic fractions were dried over MgSO4, filtered and concentrated. The residue was purified by column chromatography (0-30% EtOAc/petrol) to give the title compound (2.4 g, 67%) as a yellow solid. MS: [M+H]+=353.

Workup

  1. stirringstirred 1 h further
  2. customquenched with saturated aqueous ammonium chloride
  3. customthe two layers were separated
  4. extractionThe aqueous fraction was further extracted with EtOAc (2×20 mL)
  5. dry with materialThe combined organic fractions were dried over MgSO4
  6. filtrationfiltered
  7. concentrationconcentrated
  8. customThe residue was purified by column chromatography (0-30% EtOAc/petrol)

Sources & evidence

ORD record
ord-ff430684ba694c108941be0285a7591f
Source dataset
uspto-grants-2015_04
Patent number
US09018214B2

Reaction notes

Loading…