Sodium Carbonate → tert-butyl 4-(2-fluoropyridin-3-yl)-5,6-dihydropyridine-1(2H)-carboxylate

HRID 1846807Notes

Reaction equation

HRID 1846807 reaction equation
Br[C:2]1[C:3]([F:8])=[N:4][CH:5]=[CH:6][CH:7]=1.CC1(C)C(C)(C)OB([C:17]2[CH2:22][CH2:21][N:20]([C:23]([O:25][C:26]([CH3:29])([CH3:28])[CH3:27])=[O:24])[CH2:19][CH:18]=2)O1.C(=O)([O-])[O-].[Na+].[Na+].COCCOC.O.CCO>C(Cl)Cl.Cl[Pd](Cl)([P](C1C=CC=CC=1)(C1C=CC=CC=1)C1C=CC=CC=1)[P](C1C=CC=CC=1)(C1C=CC=CC=1)C1C=CC=CC=1>[F:8][C:3]1[C:2]([C:17]2[CH2:22][CH2:21][N:20]([C:23]([O:25][C:26]([CH3:29])([CH3:28])[CH3:27])=[O:24])[CH2:19][CH:18]=2)=[CH:7][CH:6]=[CH:5][N:4]=1

Participants

7

Reactant 4

HCID 10340Sodium CarbonateHCID 27627783-Bromo-2-fluoropyridineHCID 4642098Tert-butyl 4-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)-1,2,3,6-tetrahydropyridine-1-carboxylateHCID 86587095Dimethoxyethane ethanol water

Product 1

HCID 58547904tert-butyl 4-(2-fluoropyridin-3-yl)-5,6-dihydropyridine-1(2H)-carboxylate

Reagents, catalysts & solvents 2

HCID 178418476HCID 178418476, compoundCatalystHCID 6344DichloromethaneSolvent

Conditions

Temperature
80 °C

Procedure

3-Bromo-2-fluoropyridine (1.5 g, 8.5 mmol), tert-butyl 4-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)-5,6-dihydropyridine-1(2H)-carboxylate (3.16 g, 10.2 mmol), trans-dichlorobis(triphenylphosphine)palladium (II) (0.48 g, 0.68 mmol), sodium carbonate (4.44 g, 41.9 mmol), and 6:1:1 DME-H2O-EtOH (20 mL) were combined in a sealed tube and stirred at 80° C. for 18 h. The cooled reaction was diluted with CH2Cl2 and washed with aqueous saturated NaHCO3 solution; the aqueous layer was back-washed with CH2Cl2 (1×). The combined organic extracts were dried (MgSO4), filtered, and concentrated in vacuo. Flash column chromatography (10% to 40% EtOAc/Hexanes) gave tert-butyl 4-(2-fluoropyridin-3-yl)-5,6-dihydropyridine-1(2H)-carboxylate as a golden yellow oil. [M+1]=279.2.

Workup

  1. customThe cooled reaction
  2. washwashed with aqueous saturated NaHCO3 solution
  3. washthe aqueous layer was back-washed with CH2Cl2 (1×)
  4. dry with materialThe combined organic extracts were dried (MgSO4)
  5. filtrationfiltered
  6. concentrationconcentrated in vacuo

Sources & evidence

ORD record
ord-545dce4ebb6c4d5db2bd95532f28fe56
Source dataset
uspto-grants-2015_02
Patent number
US08952037B2

Reaction notes

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