Toluene → HCID 178455458, compound

HRID 1774724Notes

Reaction equation

HRID 1774724 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].C1(P(C2C=CC=CC=2)C2C=CC3C(=CC=CC=3)C=2C2C3C(=CC=CC=3)C=CC=2P(C2C=CC=CC=2)C2C=CC=CC=2)C=CC=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 (S)-2-((tert-butyldimethylsilyloxy)methyl)pyrrolidine (0.455 g, 2.11 mmol) in toluene (20 mL) were added tris(dibenzylideneacetone)dipalladium(0) (Pd2(dba)3) (0.039 g, 0.042 mmol) and rac-2,2′-bis(diphenylphosphino)-1,1′-binaphthalene (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 to 85° C. over night. 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 to 85° C. over night
  4. extractionthe aqueous layer was extracted with DCM (2×25 mL)
  5. washCombined organics were washed with brine
  6. dry with materialdried over Na2SO4
  7. filtrationfiltered
  8. customevaporated to dryness
  9. customThe residue was purified by silica gel flash chromatography
  10. washeluting with a 0 to 5% MeOH-DCM gradient

Sources & evidence

ORD record
ord-46634a42e67144658c87e63654a74b0a
Source dataset
uspto-grants-2016_02
Patent number
US09260408B2

Reaction notes

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