3,5-Dibromopyridine → HCID 17758932, compound

HRID 2207379Notes

Reaction equation

HRID 2207379 reaction equation
C([Mg]Cl)CCC.[Li]CCCC.Br[C:13]1[CH:14]=[N:15][CH:16]=[C:17]([Br:19])[CH:18]=1.[O:20]=[C:21]1[CH2:26][CH2:25][N:24]([C:27]([O:29][C:30]([CH3:33])([CH3:32])[CH3:31])=[O:28])[CH2:23][CH2:22]1>C1COCC1.[NH4+].[Cl-].C1(C)C=CC=CC=1>[Br:19][C:17]1[CH:18]=[C:13]([C:21]2([OH:20])[CH2:22][CH2:23][N:24]([C:27]([O:29][C:30]([CH3:32])([CH3:31])[CH3:33])=[O:28])[CH2:25][CH2:26]2)[CH:14]=[N:15][CH:16]=1

Participants

8

Reactant 4

HCID 693693,5-DibromopyridineHCID 735900tert-Butyl 4-oxopiperidine-1-carboxylateHCID 178418265HCID 178418265, compoundHCID 178418339Butyllithium

Product 1

HCID 17758932HCID 17758932, compound

Reagents, catalysts & solvents 3

HCID 1140TolueneSolvent2×HCID 8028TetrahydrofuranSolvent4×HCID 25517Ammonium ChlorideSolvent

Conditions

Temperature
-10 °C

Procedure

Literature procedure was used to for the selective monosubstitution of dibromoarenes, see: Iida, T.; Wada, T.; Tomimoto, K.; Mase, T. Tetrahedron Lett. 2001, 42, 4841-4844. n-Butylmagnesium chloride in THF (2 M, 0.739 mL, 1.48 mmol) was added to a solution of 1:1 THF:toluene (4.22 mL) and n-BuLi in hexanes (1.6M, 1.85 mL, 2.95 mmol) at −10° C. and stirred for 30 minutes. A solution of 3,5-dibromopyridine (1.00 g, 4.22 mmol) in 1:1 THF:toluene (4.22 mL) was added dropwise over 30 minutes to the reaction mixture and stirred for 1 hour at −10° C. A solution of tert-butyl 4-oxopiperidine-1-carboxylate (0.841 g, 4.22 mmol) in THF (1.00 mL) was added dropwise to the reaction mixture at −10° C. and warmed to room temperature. The reaction mixture was diluted with saturated aqueous NH4Cl and extracted with dichloromethane. The combined organic layers were dried over sodium sulfate and concentrating under reduced pressure. The crude residue was purified by silica gel chromatography (ethyl acetate/hexanes) to yield tert-butyl 4-(5-bromopyridin-3-yl)-4-hydroxypiperidine-1-carboxylate. MS APCI calc'd for C15H22BrN2O3 [M+H]+ 357 and 359. found 357 and 359.

Workup

  1. temperaturewarmed to room temperature
  2. extractionextracted with dichloromethane
  3. dry with materialThe combined organic layers were dried over sodium sulfate
  4. concentrationconcentrating under reduced pressure
  5. customThe crude residue was purified by silica gel chromatography (ethyl acetate/hexanes)

Sources & evidence

ORD record
ord-964212edb4404a0291c5fa410d9ab591
Source dataset
uspto-grants-2016_06
Patent number
US09376418B2

Reaction notes

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