Nitrogen → HCID 66974052, compound

HRID 1396027Notes

Reaction equation

HRID 1396027 reaction equation
N#N.[C:3]([O:7][C:8]([N:10]1[CH2:14][CH2:13][C:12](=[CH2:15])[CH2:11]1)=[O:9])([CH3:6])([CH3:5])[CH3:4].B1C2CCCC1CCC2.Br[C:26]1[CH:36]=[CH:35][C:29]2[O:30][C:31]([F:34])([F:33])[O:32][C:28]=2[CH:27]=1.C(=O)([O-])[O-].[K+].[K+].[OH-].[Na+]>CN(C=O)C.O.C1C=CC(P(C2C=CC=CC=2)[C-]2C=CC=C2)=CC=1.C1C=CC(P(C2C=CC=CC=2)[C-]2C=CC=C2)=CC=1.Cl[Pd]Cl.[Fe+2].O.C(Cl)Cl>[C:3]([O:7][C:8]([N:10]1[CH2:14][CH2:13][CH:12]([CH2:15][C:36]2[CH:26]=[CH:27][C:28]3[O:32][C:31]([F:33])([F:34])[O:30][C:29]=3[CH:35]=2)[CH2:11]1)=[O:9])([CH3:6])([CH3:5])[CH3:4]

Participants

11

Reactant 6

HCID 947NitrogenHCID 11430Potassium CarbonateHCID 14798Sodium HydroxideHCID 789669-Borabicyclo(3.3.1)nonaneHCID 27362715-Bromo-2,2-difluoro-1,3-benzodioxoleHCID 15297967tert-Butyl 3-methylidenepyrrolidine-1-carboxylate

Product 1

HCID 66974052HCID 66974052, compoundYield 96.7%

Reagents, catalysts & solvents 4

HCID 178418228Bis(cyclopenta-1,4-dien-1-yl(diphenyl)phosphane);dichloropalladium;iron(2+)CatalystHCID 962WaterSolventHCID 6344DichloromethaneSolventHCID 21962138N,N-Dimethylformamide--water (1/1)Solvent

Procedure

A stream of N2 was bubbled through neat 3-methylene pyrrolidine-1-carboxylic acid tert-butyl ester (792 mg, 4.33 mmol) for 15 min before charging the flask with 9-BBN (0.5 M in THF, 8.8 mL). The reaction mixture was heated at reflux for 2.5 h; then cooled to rt. The resultant mixture was then added, via cannula, to a preformed solution consisting of 5-bromo-2,2-difluoro-1,3-benzodioxole (1.01 g, 4.24 mmol), Pd(dppf)Cl2.CH2Cl2 (92 mg), and potassium carbonate (760 mg, 5.50 mmol) in DMF/H2O (10 mL/1 mL). The reaction mixture was heated at 60° C. for 18 h, cooled to rt and poured into water. The pH of the mixture was adjusted to 11 with NaOH (1 N), and extracted with EtOAc (3×). The organic layers were combined, dried (Na2SO4), and concentrated. The crude residue was purified (FCC) to give the title compound (1.4 g, 94%).

Workup

  1. temperatureThe reaction mixture was heated
  2. temperatureat reflux for 2.5 h
  3. temperatureThe reaction mixture was heated at 60° C. for 18 h
  4. temperaturecooled to rt
  5. extractionextracted with EtOAc (3×)
  6. dry with materialdried (Na2SO4)
  7. concentrationconcentrated
  8. customThe crude residue was purified (FCC)

Sources & evidence

ORD record
ord-6f228b1399c448298ce39470bea8270b
Source dataset
uspto-grants-2014_12
Patent number
US08901111B2

Reaction notes

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