Dichloromethane → racemic tert-butyl 3,5'-dichloro-2'-fluoro-2,4'-bipyridin-6-yl((tetrahydro-2H-pyran-3-yl)methyl)carbamate

HRID 1623407Notes

Reaction equation

HRID 1623407 reaction equation
Br[C:2]1[N:7]=[C:6]([N:8]([CH2:16][CH:17]2[CH2:22][CH2:21][CH2:20][O:19][CH2:18]2)[C:9](=[O:15])[O:10][C:11]([CH3:14])([CH3:13])[CH3:12])[CH:5]=[CH:4][C:3]=1[Cl:23].[Cl:24][C:25]1[C:26](B(O)O)=[CH:27][C:28]([F:31])=[N:29][CH:30]=1.C(Cl)Cl.C([O-])([O-])=O.[Na+].[Na+]>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].O.COCCOC>[Cl:23][C:3]1[C:2]([C:26]2[C:25]([Cl:24])=[CH:30][N:29]=[C:28]([F:31])[CH:27]=2)=[N:7][C:6]([N:8]([CH2:16][CH:17]2[CH2:22][CH2:21][CH2:20][O:19][CH2:18]2)[C:9](=[O:15])[O:10][C:11]([CH3:14])([CH3:13])[CH3:12])=[CH:5][CH:4]=1

Participants

8

Reactant 4

HCID 6344DichloromethaneHCID 10340Sodium CarbonateHCID 44754822(5-Chloro-2-fluoropyridin-4-yl)boronic acidHCID 87210765HCID 87210765, compound

Product 1

HCID 66937007racemic tert-butyl 3,5'-dichloro-2'-fluoro-2,4'-bipyridin-6-yl((tetrahydro-2H-pyran-3-yl)methyl)carbamateYield 40%

Reagents, catalysts & solvents 3

HCID 178418228Bis(cyclopenta-1,4-dien-1-yl(diphenyl)phosphane);dichloropalladium;iron(2+)CatalystHCID 962WaterSolventHCID 80711,2-DimethoxyethaneSolvent

Conditions

Temperature
90 °C

Procedure

To a scintillation vial was added racemic tert-butyl 6-bromo-5-chloropyridin-2-yl((tetrahydro-2H-pyran-3-yl)methyl)carbamate (832 mg, 2.051 mmol), 5-chloro-2-fluoropyridin-4-ylboronic acid (719 mg, 4.10 mmol) and PdCl2(dppf).CH2Cl2 adduct (167 mg, 0.205 mmol) followed by DME (3 mL) and 2M Na2CO3 aq (2 mL). The mixture was heated at 90° C. for 20 h, then allowed to cool and added water and then extracted with EtOAc (×3). The organics were washed with water (×2), saturated brine (×2), then dried (Na2SO4), filtered and evaporated under reduced pressure. The resulting residue was purified by flash column chromatography (silica gel; 5% to 15% EtOAc/heptanes) to give racemic tert-butyl 3,5′-dichloro-2′-fluoro-2,4′-bipyridin-6-yl((tetrahydro-2H-pyran-3-yl)methyl)carbamate (374 mg)

Workup

  1. temperatureto cool
  2. extractionextracted with EtOAc (×3)
  3. washThe organics were washed with water (×2), saturated brine (×2)
  4. dry with materialdried (Na2SO4)
  5. filtrationfiltered
  6. customevaporated under reduced pressure
  7. customThe resulting residue was purified by flash column chromatography (silica gel; 5% to 15% EtOAc/heptanes)

Sources & evidence

ORD record
ord-240d52ebfcb8420192b8207b608547ac
Source dataset
uspto-grants-2014_07
Patent number
US08778951B2

Reaction notes

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