4-Bromobenzoyl chloride → (R)-tert-butyl 3-(4-bromo-N-(3-chloropyridin-2-yl)benzamido)piperidine-1-carboxylate

HRID 588366Notes

Reaction equation

HRID 588366 reaction equation
[Cl:1][C:2]1[C:3]([NH:8][C@@H:9]2[CH2:14][CH2:13][CH2:12][N:11]([C:15]([O:17][C:18]([CH3:21])([CH3:20])[CH3:19])=[O:16])[CH2:10]2)=[N:4][CH:5]=[CH:6][CH:7]=1.[Br:22][C:23]1[CH:31]=[CH:30][C:26]([C:27](Cl)=[O:28])=[CH:25][CH:24]=1.C[Si]([N-][Si](C)(C)C)(C)C.[Li+]>C1COCC1>[Br:22][C:23]1[CH:31]=[CH:30][C:26]([C:27]([N:8]([C:3]2[C:2]([Cl:1])=[CH:7][CH:6]=[CH:5][N:4]=2)[C@@H:9]2[CH2:14][CH2:13][CH2:12][N:11]([C:15]([O:17][C:18]([CH3:21])([CH3:20])[CH3:19])=[O:16])[CH2:10]2)=[O:28])=[CH:25][CH:24]=1

Participants

5

Reactant 3

HCID 685154-Bromobenzoyl chlorideHCID 2733832Lithium HexamethyldisilazideHCID 117652951(R)-tert-butyl 3-((3-chloropyridin-2-yl)amino)piperidine-1-carboxylate

Product 1

HCID 117652956(R)-tert-butyl 3-(4-bromo-N-(3-chloropyridin-2-yl)benzamido)piperidine-1-carboxylateYield 63%

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent

Procedure

To a solution of Preparation 1 (R)-tert-butyl 3-((3-chloropyridin-2-yl)amino)piperidine-1-carboxylate (100 g, 321 mmol) and 4-bromobenzoyl chloride (73.7 g, 336 mmol) in dry THF (500 mL) was added 1 M lithium bis(trimethylsilyl)amide (362 mL, 362 mmol) dropwise at 0° C. The reaction mixture was warmed and stirred at room temperature overnight. The reaction was quenched with water and extracted with EtOAc (3×1000 mL). The combined organic layers were washed with brine, dried over Na2SO4, filtered and the filtrate was concentrated in vacuo. The residue was purified by chromatography on silica gel to give afford the title compound as a yellow solid (100 g, 63%).

Workup

  1. temperatureThe reaction mixture was warmed
  2. customThe reaction was quenched with water
  3. extractionextracted with EtOAc (3×1000 mL)
  4. washThe combined organic layers were washed with brine
  5. dry with materialdried over Na2SO4
  6. filtrationfiltered
  7. concentrationthe filtrate was concentrated in vacuo
  8. customThe residue was purified by chromatography on silica gel
  9. customto give

Sources & evidence

ORD record
ord-3cb1a19fe0ad4f3e931ed9913c47d9fc
Source dataset
uspto-grants-2016_01
Patent number
US09227956B2

Reaction notes

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