Toluene → HCID 178455458, compound

HRID 2277669Notes

Reaction equation

HRID 2277669 reaction equation
[Si:1]([O:8]C[C@@H]1CCCN1)([C:4]([CH3:7])([CH3:6])[CH3:5])(C)C.CC(C)([O-])C.[Na+].Br[C:22]1[CH:23]=[N:24][CH:25]=[C:26]([Br:28])[CH:27]=1.[NH4+:29].[Cl-].[C:31]1([CH3:37])[CH:36]=[CH:35][CH:34]=[CH:33][CH:32]=1>C1C=CC(/C=C/C(/C=C/C2C=CC=CC=2)=O)=CC=1.C1C=CC(/C=C/C(/C=C/C2C=CC=CC=2)=O)=CC=1.C1C=CC(/C=C/C(/C=C/C2C=CC=CC=2)=O)=CC=1.[Pd].[Pd].C1C=CC(P(C2C(C3C(P(C4C=CC=CC=4)C4C=CC=CC=4)=CC=C4C=3C=CC=C4)=C3C(C=CC=C3)=CC=2)C2C=CC=CC=2)=CC=1>[Br:28][C:26]1[CH:25]=[N:24][CH:23]=[C:22]([N:29]2[CH2:33][CH2:34][CH2:35][C@H:36]2[C:31]([CH3:32])([CH3:37])[O:8][SiH2:1][C:4]([CH3:7])([CH3:6])[CH3:5])[CH:27]=1

Participants

8

Reactant 5

HCID 1140TolueneHCID 25517Ammonium ChlorideHCID 693693,5-DibromopyridineHCID 11275950(S)-2-(((tert-Butyldimethylsilyl)oxy)methyl)pyrrolidineHCID 23676156Sodium t-butoxide

Product 1

HCID 178455458HCID 178455458, compoundYield 53%

Reagents, catalysts & solvents 2

HCID 634876Binap, (A+-)-CatalystHCID 9811564Bis(dibenzylideneacetone)palladiumCatalyst

Conditions

Temperature
85 °C

Procedure

To a solution of crude (S)-2-((tert-butyldimethylsilyloxy)methyl)pyrrolidine (0.455 g, 2.11 mmol) in toluene (20 mL) were added Pd2(dba)3 (0.039 g, 0.042 mmol) and rac-BINAP (0.066 g, 0.106 mmol). The solution was purged with argon and heated to 85° C. for 10 min. After cooling to room temperature, sodium tert-butoxide (0.406 g, 4.22 mmol) and 3,5-dibromopyridine (0.5 g, 2.11 mmol) were added and the reaction mixture was then heated at 85° C. overnight. The mixture was poured into sat NH4Cl (20 mL) and the aqueous layer was extracted with DCM (2×25 mL). Combined organics were washed with brine, dried over Na2SO4, filtered and evaporated to dryness. The residue was purified by silica gel flash chromatography eluting with a 0 to 5% MeOH-DCM gradient to give the title compound (0.412 g, 53%) as a yellow oil. MS: 371.0, 372.9 (M+H+).

Workup

  1. customThe solution was purged with argon
  2. temperatureAfter cooling to room temperature
  3. temperaturethe reaction mixture was then heated at 85° C. overnight
  4. additionThe mixture was poured
  5. extractionthe aqueous layer was extracted with DCM (2×25 mL)
  6. washCombined organics were washed with brine
  7. dry with materialdried over Na2SO4
  8. filtrationfiltered
  9. customevaporated to dryness
  10. customThe residue was purified by silica gel flash chromatography
  11. washeluting with a 0 to 5% MeOH-DCM gradient

Sources & evidence

ORD record
ord-d2dc6d89393142b6a0b1b1bb1d5236b0
Source dataset
uspto-grants-2015_09
Patent number
US09133158B2

Reaction notes

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