Citric Acid → 6-(2-Fluoro-benzyl)-3,3-dimethyl-2,3-dihydro-pyrrolo[3,2-b]pyridine-1-carboxylic acid tert-butyl ester

HRID 1475506Notes

Reaction equation

HRID 1475506 reaction equation
[C:1]([O:5][C:6]([N:8]1[C:16]2[C:11](=[N:12][CH:13]=[C:14](Br)[CH:15]=2)[C:10]([CH3:19])([CH3:18])[CH2:9]1)=[O:7])([CH3:4])([CH3:3])[CH3:2].[Br-].[Li+].[Cl-].[F:23][C:24]1[CH:31]=[CH:30][CH:29]=[CH:28][C:25]=1[CH2:26][Zn+].C(O)(=O)CC(CC(O)=O)(C(O)=O)O>C(N1C=CN(C(C)C)C1=[Pd-3](Cl)(Cl)C1C(Cl)=CC=CN=1)(C)C.O.C1COCC1.CN1CCCC1=O>[C:1]([O:5][C:6]([N:8]1[C:16]2[C:11](=[N:12][CH:13]=[C:14]([CH2:26][C:25]3[CH:28]=[CH:29][CH:30]=[CH:31][C:24]=3[F:23])[CH:15]=2)[C:10]([CH3:19])([CH3:18])[CH2:9]1)=[O:7])([CH3:4])([CH3:3])[CH3:2]

Participants

9

Reactant 4

HCID 311Citric AcidHCID 82050Lithium BromideHCID 70980192HCID 70980192, compoundHCID 178505630HCID 178505630, compound

Product 1

HCID 709820396-(2-Fluoro-benzyl)-3,3-dimethyl-2,3-dihydro-pyrrolo[3,2-b]pyridine-1-carboxylic acid tert-butyl esterYield 96%

Reagents, catalysts & solvents 4

HCID 178456358HCID 178456358, compoundCatalystHCID 962WaterSolventHCID 8028TetrahydrofuranSolvent2×HCID 13387N-methyl-2-pyrrolidoneSolvent

Conditions

Temperature
20 °C

Procedure

To a nitrogen-degassed mixture of 6-bromo-3,3-dimethyl-2,3-dihydro-pyrrolo[3,2-b]pyridine-1-carboxylic acid tert-butyl ester (4.09 g, 12.5 mmol), lithium bromide (3.22 g, 37.5 mmol), (1,3-diisopropylimidazol-2-ylidene)(3-chloropyridyl)palladium (II) dichloride (0.17 g, 0.25 mmol), 1-methyl-2-pyrrolidinone (30 mL) and THF (30 mL) was added a solution of 2-fluoro- benzylzinc chloride in THF (0.5 M, 40 mL, 20 mmol) and resulting mixture was stirred at 20° C. for 3 h. The mixture was poured into water (150 mL) and 5% aqueous citric acid (30 mL) and the resulting mixture extracted with Et2O (3×70 mL). The organic phase was washed with water (100 mL), brine (3×100 mL), dried (MgSO4) and evaporated in vacuo to give an oil. Chromatography (SiO2, eluted with petrol-EtOAc 0-30%) gave the title compound (4.29 g 96%) as an oil. MS: [M+H]+=357.

Workup

  1. customTo a nitrogen-degassed
  2. customresulting mixture
  3. extractionthe resulting mixture extracted with Et2O (3×70 mL)
  4. washThe organic phase was washed with water (100 mL), brine (3×100 mL)
  5. dry with materialdried (MgSO4)
  6. customevaporated in vacuo
  7. customto give an oil
  8. washChromatography (SiO2, eluted with petrol-EtOAc 0-30%)

Sources & evidence

ORD record
ord-23734c4a8e9a493a824291bba8bfc9b0
Source dataset
uspto-grants-2015_04
Patent number
US09018214B2

Reaction notes

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