Sodium Carbonate → 2-chloro-3-(3,6-dihydro-2H-pyran-4-yl)pyridine

HRID 454892Notes

Reaction equation

HRID 454892 reaction equation
Br[C:2]1[C:3]([Cl:8])=[N:4][CH:5]=[CH:6][CH:7]=1.CC1(C)C(C)(C)CB([C:17]2[CH2:18][CH2:19][O:20][CH2:21][CH:22]=2)C1.C([O-])([O-])=O.[Na+].[Na+]>O1CCOCC1.O.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:8][C:3]1[C:2]([C:17]2[CH2:22][CH2:21][O:20][CH2:19][CH:18]=2)=[CH:7][CH:6]=[CH:5][N:4]=1

Participants

7

Reactant 3

HCID 10340Sodium CarbonateHCID 6933243-Bromo-2-chloropyridineHCID 674787471-(3,6-Dihydro-2H-pyran-4-yl)-3,3,4,4-tetramethylborolane

Product 1

HCID 585477502-chloro-3-(3,6-dihydro-2H-pyran-4-yl)pyridineYield 131.5%

Reagents, catalysts & solvents 3

HCID 178418228Bis(cyclopenta-1,4-dien-1-yl(diphenyl)phosphane);dichloropalladium;iron(2+)CatalystHCID 962WaterSolventHCID 312751,4-DioxaneSolvent

Conditions

Temperature
110 °C

Procedure

To a solution of 3-bromo-2-chloropyridine (4 g, 10.8 mmol), 4-(3,3,4,4-tetramethyl-borolan-1-yl)-3,6-dihydro-2H-pyran (5.7 g, 13.1 mmol) and Na2CO3 (2.28 g, 21.6 mmol) in 1,4-dioxane (60 mL) and H2O (6 mL) was added Pd(dppf)Cl2 (410 mg, 0.56 mmol). The reaction mixture was stirred at 110° C. under N2 for overnight. The reaction mixture was filtered through CELITE® and washed CH2Cl2. The organic layers were concentrated to give the crude product which was purified by silica gel column chromatography to give the title compound (3.5 g, 14.2 mmol, 70% yield).

Workup

  1. filtrationThe reaction mixture was filtered through CELITE®
  2. washwashed CH2Cl2
  3. concentrationThe organic layers were concentrated
  4. customto give the crude product which
  5. customwas purified by silica gel column chromatography

Sources & evidence

ORD record
ord-60d5635f8c094ca89567576722cecb25
Source dataset
uspto-grants-2013_07
Patent number
US08497265B2

Reaction notes

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