2-Bromopyridine → HCID 118497059, compound

HRID 522142Notes

Reaction equation

HRID 522142 reaction equation
[Cl:1][C:2]1[CH:11]=[C:10]([O:12][CH3:13])[C:9](B2OC(C)(C)C(C)(C)O2)=[CH:8][C:3]=1[C:4]([O:6][CH3:7])=[O:5].O1CCOCC1.C([O-])([O-])=O.[Na+].[Na+].Br[C:36]1[CH:41]=[CH:40][CH:39]=[CH:38][N:37]=1>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]>[Cl:1][C:2]1[CH:11]=[C:10]([O:12][CH3:13])[C:9]([C:36]2[CH:41]=[CH:40][CH:39]=[CH:38][N:37]=2)=[CH:8][C:3]=1[C:4]([O:6][CH3:7])=[O:5]

Participants

6

Reactant 4

HCID 79732-BromopyridineHCID 10340Sodium CarbonateHCID 312751,4-DioxaneHCID 123512686HCID 123512686, compound

Product 1

HCID 118497059HCID 118497059, compoundYield 35%

Reagents, catalysts & solvents 1

HCID 178418228Bis(cyclopenta-1,4-dien-1-yl(diphenyl)phosphane);dichloropalladium;iron(2+)Catalyst

Procedure

To a solution of methyl 2-chloro-4-methoxy-5-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)benzoate in dioxane (Preparation 47, 935 mg, 2.86 mmol) was added 2M Na2CO3 (4.30 mL, 8.58 mmol) and stirred for 15 minutes at room temperature. 2-bromopyridine (542 mg, 3.43 mmol) was added and the reaction was purged with nitrogen for 15 minutes. Pd(dppf)Cl2 (117 mg, 0.14 mmol) was added and the reaction heated at 110° C. for 2 hours. The reaction was cooled to room temperature, filtered through arbocel and washed with EtOAc (50 mL). The filtrate was washed with brine (50 mL) and the aqueous layer was re-extracted with EtOAc (50 mL). The combined organic layers were dried over magnesium sulphate and concentrated in vacuo. The residue was purified using silica gel column chromatography eluting with 10-20% EtOAc in heptanes to afford the title compound (282 mg, 35% over 2 steps).

Workup

  1. customthe reaction was purged with nitrogen for 15 minutes
  2. temperaturethe reaction heated at 110° C. for 2 hours
  3. temperatureThe reaction was cooled to room temperature
  4. filtrationfiltered through arbocel
  5. washwashed with EtOAc (50 mL)
  6. washThe filtrate was washed with brine (50 mL)
  7. extractionthe aqueous layer was re-extracted with EtOAc (50 mL)
  8. dry with materialThe combined organic layers were dried over magnesium sulphate
  9. concentrationconcentrated in vacuo
  10. customThe residue was purified
  11. washeluting with 10-20% EtOAc in heptanes

Sources & evidence

ORD record
ord-94af4d1aec8944a49b3b4613964be398
Source dataset
uspto-grants-2016_05
Patent number
US09328096B2

Reaction notes

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