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

HRID 1475437Notes

Reaction equation

HRID 1475437 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:32])[CH2:29][CH2:30][CH3:31]>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:32])[CH2:29][CH2:30][CH3:31])[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 13704543N-Methoxy-N-methylbutyramideHCID 70980192HCID 70980192, compoundHCID 178418339Butyllithium

Product 1

HCID 709802516-Butyryl-3,3-dimethyl-2,3-dihydro-pyrrolo[3,2-b]pyridine-1-carboxylic acid tert-butyl esterYield 72%

Reagents, catalysts & solvents 1

HCID 3283Diethyl EtherSolvent2×

Procedure

Butyllithium (12.0 mL, 2.5 M solution in hexanes, 30 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 (8.0 g, 24.5 mmol) in diethyl ether (80 mL) at −78° C. The resulting orange slurry was stirred 30 minutes at this temperature before a solution of N-methoxy-N-methylbutyramide (prepared in a manner similar to that described in US2010/060696) (5.3 g, 36.6 mmol) in diethyl ether (40 mL) was added dropwise over 1 h. 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 (2×50 mL). The combined organic fractions were dried over MgSO4, filtered and concentrated. Chromatography (0-30% EtOAc/petrol) gave the title compound (5.6 g, 72%) as a yellow solid. MS: [M+H]+=319.

Workup

  1. customprepared in a manner similar to
  2. additionwas added dropwise over 1 h
  3. customquenched with saturated aqueous ammonium chloride
  4. customthe two layers were separated
  5. extractionThe aqueous fraction was further extracted with EtOAc (2×50 mL)
  6. dry with materialThe combined organic fractions were dried over MgSO4
  7. filtrationfiltered
  8. concentrationconcentrated

Sources & evidence

ORD record
ord-426a67e349804881b2217a8f6cff3150
Source dataset
uspto-grants-2015_04
Patent number
US09018214B2

Reaction notes

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