Citric Acid → 6-(4-Fluoro-benzyl)-3,3-dimethyl-2,3-dihydro-pyrrolo[3,2-b]pyridine-1-carboxylic acid tert-butyl ester

HRID 1475498Notes

Reaction equation

HRID 1475498 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][C:27]([CH2:28][Zn+])=[CH:26][CH:25]=1.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]([CH2:28][C:27]3[CH:30]=[CH:31][C:24]([F:23])=[CH:25][CH:26]=3)[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 178505764HCID 178505764, compound

Product 1

HCID 709812016-(4-Fluoro-benzyl)-3,3-dimethyl-2,3-dihydro-pyrrolo[3,2-b]pyridine-1-carboxylic acid tert-butyl esterYield 99%

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 (3.27 g, 10.0 mmol), lithium bromide (2.58 g, 30.0 mmol), (1,3-diisopropylimidazol-2-ylidene)(3-chloropyridyl)palladium (II) dichloride (0.136 g, 0.2 mmol), 1-methyl-2-pyrrolidinone (30 mL) and THF (30 mL) was added a solution of 4-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 (3.5 g, 99%) 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-1daaf08f2d7c42ed9b761d0cf0a05885
Source dataset
uspto-grants-2015_04
Patent number
US09018214B2

Reaction notes

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