2-Bromopyridine → tert-Butyl 5',6'-dihydro-[2,4'-bipyridine]-1'(2'H)-carboxylate

HRID 406485Notes

Reaction equation

HRID 406485 reaction equation
CC1(C)C(C)(C)OB([C:9]2[CH2:14][CH2:13][N:12]([C:15]([O:17][C:18]([CH3:21])([CH3:20])[CH3:19])=[O:16])[CH2:11][CH:10]=2)O1.Br[C:24]1[CH:29]=[CH:28][CH:27]=[CH:26][N:25]=1.C(=O)([O-])[O-].[Na+].[Na+]>COCCOC.O.C1C=CC([P]([Pd]([P](C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)([P](C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)[P](C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)=CC=1>[N:25]1[CH:26]=[CH:27][CH:28]=[CH:29][C:24]=1[C:9]1[CH2:14][CH2:13][N:12]([C:15]([O:17][C:18]([CH3:19])([CH3:20])[CH3:21])=[O:16])[CH2:11][CH:10]=1

Participants

7

Reactant 3

HCID 79732-BromopyridineHCID 10340Sodium CarbonateHCID 4642098Tert-butyl 4-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)-1,2,3,6-tetrahydropyridine-1-carboxylate

Product 1

HCID 16094711tert-Butyl 5',6'-dihydro-[2,4'-bipyridine]-1'(2'H)-carboxylateYield 74.6%

Reagents, catalysts & solvents 3

HCID 178418397HCID 178418397, compoundCatalystHCID 962WaterSolventHCID 80711,2-DimethoxyethaneSolvent

Conditions

Temperature
85 °C

Procedure

A mixture of tert-butyl 4-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)-5,6-dihydropyridine-1(2H)-carboxylate (0.500 g, 1.04 mmol), 2-bromopyridine (0.164 g, 1.04 mmol), sodium carbonate (0.439 g, 4.14 mmol), tetrakis(triphenylphosphine)palladium(0) (0.120 g, 0.103 mmol) in ethylene glycol dimethyl ether (20 mL) and water (10 mL) was heated at about 85° C. for about 12 hours. The reaction mixture was allowed to cool to ambient temperature and the solvent was removed under reduced pressure. The residue was partitioned between water (25 mL) and dichloromethane (50 mL). The organic layer was separated and the aqueous layer was further extracted with dichloromethane (2×50 mL). The combined organic extracts were dried over magnesium sulfate and evaporated under reduced pressure. The residue was purified by using preparative RP-HPLC (Rainin C18, 8 mm, 300 Å, 35 cm; 5-100% acetonitrile—0.1M ammonium acetate over 20 min, 100% acetonitrile hold 10 minutes, 21 mL/min) to give tert-butyl 4-(pyridin-2-yl)-5,6-dihydropyridine-1(2H)-carboxylate (0.202 g, 0.776 mmol) as a white solid; RP-HPLC (Table 1, Method b) Rt 2.78 min; m/z: (M+H)+ 261.

Workup

  1. temperatureto cool to ambient temperature
  2. customthe solvent was removed under reduced pressure
  3. customThe residue was partitioned between water (25 mL) and dichloromethane (50 mL)
  4. customThe organic layer was separated
  5. extractionthe aqueous layer was further extracted with dichloromethane (2×50 mL)
  6. dry with materialThe combined organic extracts were dried over magnesium sulfate
  7. customevaporated under reduced pressure
  8. customThe residue was purified
  9. customRP-HPLC (Rainin C18, 8 mm, 300 Å, 35 cm; 5-100% acetonitrile—0.1M ammonium acetate over 20 min, 100% acetonitrile hold 10 minutes, 21 mL/min)

Sources & evidence

ORD record
ord-f3bb24cb4955421c84f7d08d95d76b71
Source dataset
uspto-grants-2014_06
Patent number
US08754107B2

Reaction notes

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