Nitrogen → HCID 66974058, compound

HRID 1396031Notes

Reaction equation

HRID 1396031 reaction equation
N#N.[C:3]([O:7][C:8]([N:10]1[CH2:14][CH2:13][CH:12]([CH:15]=[CH2:16])[CH2:11]1)=[O:9])([CH3:6])([CH3:5])[CH3:4].B1C2CCCC1CCC2.Br[C:27]1[CH:37]=[CH:36][C:30]2[O:31][C:32]([F:35])([F:34])[O:33][C:29]=2[CH:28]=1.C(Cl)Cl.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:3]([O:7][C:8]([N:10]1[CH2:14][CH2:13][CH:12]([CH2:15][CH2:16][C:37]2[CH:27]=[CH:28][C:29]3[O:33][C:32]([F:34])([F:35])[O:31][C:30]=3[CH:36]=2)[CH2:11]1)=[O:9])([CH3:6])([CH3:5])[CH3:4]

Participants

11

Reactant 7

HCID 947NitrogenHCID 6344DichloromethaneHCID 11430Potassium CarbonateHCID 14798Sodium HydroxideHCID 789669-Borabicyclo(3.3.1)nonaneHCID 27362715-Bromo-2,2-difluoro-1,3-benzodioxoleHCID 53302213tert-Butyl 3-ethenylpyrrolidine-1-carboxylate

Product 1

HCID 66974058HCID 66974058, compoundYield 98%

Reagents, catalysts & solvents 3

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

Procedure

A stream of N2 was bubbled through neat 3-vinyl-pyrrolidine-1-carboxylic acid tert-butyl ester (589 mg, 2.99 mmol) for 15 min before adding 9-BBN (0.5 M in THF, 6 mL). The reaction mixture was heated at reflux for 2 h, then cooled to rt. The reaction mixture was then added, via cannula, to a preformed solution consisting of 5-bromo-2,2-difluoro-1,3-benzodioxole (704 mg, 2.97 mmol), Pd(dppf)Cl2.CH2Cl2 (69.7 mg, 0.0953 mmol), and potassium carbonate (559 mg, 4.04 mmol) in DMF/H2O (10 mL/1 mL). The resultant 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 (1.0 g, 98%).

Workup

  1. temperatureThe reaction mixture was heated
  2. temperatureat reflux for 2 h
  3. additionThe reaction mixture was then added, via cannula, to a preformed solution
  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-c2af606677024e008e8fb05d402e9b3b
Source dataset
uspto-grants-2014_12
Patent number
US08901111B2

Reaction notes

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