Citric Acid → HCID 70980775, compound

HRID 1475359Notes

Reaction equation

HRID 1475359 reaction equation
[C:1]([O:5][C:6]([N:8]1[C:16]2[CH:15]=[C:14](Cl)[N:13]=[CH:12][C:11]=2[C:10]([CH3:19])([CH3:18])[CH2:9]1)=[O:7])([CH3:4])([CH3:3])[CH3:2].[Br-].[Li+].[Br-].[CH2:23]([Zn+])[C:24]1[CH:29]=[CH:28][CH:27]=[CH:26][CH:25]=1.C(O)(=O)CC(CC(O)=O)(C(O)=O)O>C1COCC1.C(N1C=CN(C(C)C)C1=[Pd-3](Cl)(Cl)C1C(Cl)=CC=CN=1)(C)C.O.CN1CCCC1=O>[C:1]([O:5][C:6]([N:8]1[C:16]2[CH:15]=[C:14]([CH2:23][C:24]3[CH:29]=[CH:28][CH:27]=[CH:26][CH:25]=3)[N:13]=[CH:12][C:11]=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 86723969tert-Butyl 6-chloro-3,3-dimethyl-2,3-dihydro-1H-pyrrolo[3,2-c]pyridine-1-carboxylateHCID 178419772HCID 178419772, compound

Product 1

HCID 70980775HCID 70980775, compound

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-chloro-3,3-dimethyl-2,3-dihydro-pyrrolo[3,2-c]pyridine-1-carboxylic acid tert-butyl ester (1.12 g, 4 mmol), lithium bromide (1.39 g, 16 mmol), (1,3-diisopropylimidazol-2-ylidene)(3-chloropyridyl)palladium (II) dichloride (0.056 g, 0.08 mmol), 1-methyl-2-pyrrolidinone (10 mL) and THF (10 mL) was added a solution of benzylzinc bromide in THF (0.5 M, 32 mL) and resulting mixture was stirred at 20° C. for 24 h. The mixture was poured into water (100 mL) and 5% aqueous citric acid (30 mL) and the resulting mixture extracted with 1:1 EtOAc-petrol. The organic phase was washed with water (3×50 mL), dried (Na2SO4) and evaporated in vacuo to give an oil. Chromatography (SiO2, eluted with petrol-Et2O 0-80%) gave the title compound (1.1 g) as an oil. 1H NMR (CDCl3): 8.20 (1H, s), 7.32 (4H, d), 7.27-7.03 (2H, m), 4.13 (2H, s), 3.71 (2H, s), 1.51 (9H, s), 1.37 (6H, s).

Workup

  1. customTo a nitrogen-degassed
  2. customresulting mixture
  3. extractionthe resulting mixture extracted with 1:1 EtOAc-petrol
  4. washThe organic phase was washed with water (3×50 mL)
  5. dry with materialdried (Na2SO4)
  6. customevaporated in vacuo
  7. customto give an oil
  8. washChromatography (SiO2, eluted with petrol-Et2O 0-80%)

Sources & evidence

ORD record
ord-6aa8bacc5cb642669525dfafb6d056fa
Source dataset
uspto-grants-2015_04
Patent number
US09018214B2

Reaction notes

Loading…