2-Bromopyridine → HCID 131731658, compound

HRID 1621001Notes

Reaction equation

HRID 1621001 reaction equation
Br[C:2]1[CH:7]=CC=C[N:3]=1.[CH2:8]([Li])[CH2:9][CH2:10][CH3:11].C([C:15]1([C:28]2[CH:33]=[CH:32][C:31]([Cl:34])=[C:30]([Cl:35])[CH:29]=2)[CH2:20][CH2:19][N:18]([C:21]([O:23][C:24]([CH3:27])([CH3:26])[CH3:25])=[O:22])[CH2:17][CH2:16]1)#N.C1C[O:39]CC1>[NH4+].[Cl-]>[Cl:35][C:30]1[CH:29]=[C:28]([C:15]2([C:20]([CH:19]3[CH2:11][CH2:10][CH2:9][CH2:8][N:18]3[C:21]([O:23][C:24]([CH3:26])([CH3:27])[CH3:25])=[O:22])=[O:39])[CH:16]=[CH:17][NH:3][CH:2]=[CH:7]2)[CH:33]=[CH:32][C:31]=1[Cl:34]

Participants

6

Reactant 4

HCID 79732-BromopyridineHCID 8028Tetrahydrofuran2×HCID 49760263tert-Butyl 4-cyano-4-(3,4-dichlorophenyl)piperidine-1-carboxylateHCID 178418339Butyllithium

Product 1

HCID 131731658HCID 131731658, compound

Reagents, catalysts & solvents 1

HCID 25517Ammonium ChlorideSolvent

Procedure

To a solution of 2-bromopyridine (0.768 g, 4.86 mmol) in dry THF (20 mL) was added n-butyllithium (2.5 M in hexane, 0.6 mL, 4.86 mmol) at −78° C. After stirring for 30 minutes, the solution of Example 140A (1.2 g, 3.24 mmol) in THF (5 mL) was added. The mixture was stirred at −78° C. for 30 minutes, diluted with saturated NH4Cl (2×20 mL) and extracted with EtOAc (2×20 mL). The combined organic layers were dried over Na2SO4, filtered, and concentrated. The resulting residue was purified by column chromatography on silica gel (petroleum ether/EtOAc=10/1) to give Example 140B.

Workup

  1. stirringThe mixture was stirred at −78° C. for 30 minutes
  2. extractionextracted with EtOAc (2×20 mL)
  3. dry with materialThe combined organic layers were dried over Na2SO4
  4. filtrationfiltered
  5. concentrationconcentrated
  6. customThe resulting residue was purified by column chromatography on silica gel (petroleum ether/EtOAc=10/1)
  7. customto give Example 140B

Sources & evidence

ORD record
ord-e8ff502f875a4995bd4390eba3d1cfbc
Source dataset
uspto-grants-2014_07
Patent number
US08772500B2

Reaction notes

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