Ammonium Chloride → 4-[2-(5-Bromo-2-chloro-pyridin-4-yl)-1-hydroxy-1-methyl-ethyl]-piperidine-1-carboxylic acid tert-butyl ester

HRID 533123Notes

Reaction equation

HRID 533123 reaction equation
[C:1]([O:5][C:6]([N:8]1[CH2:13][CH2:12][CH:11]([C:14](=[O:24])[CH2:15][C:16]2[C:21]([Br:22])=[CH:20][N:19]=[C:18]([Cl:23])[CH:17]=2)[CH2:10][CH2:9]1)=[O:7])([CH3:4])([CH3:3])[CH3:2].[CH3:25][Mg]Br.[NH4+].[Cl-]>O1CCCC1>[C:1]([O:5][C:6]([N:8]1[CH2:9][CH2:10][CH:11]([C:14]([OH:24])([CH3:25])[CH2:15][C:16]2[C:21]([Br:22])=[CH:20][N:19]=[C:18]([Cl:23])[CH:17]=2)[CH2:12][CH2:13]1)=[O:7])([CH3:4])([CH3:2])[CH3:3]

Participants

5

Reactant 3

HCID 25517Ammonium ChlorideHCID 866748944-[2-(5-Bromo-2-chloropyridin-4-yl)acetyl]piperidine-1-carboxylic acid tert-butyl esterHCID 178418573HCID 178418573, compound

Product 1

HCID 866748994-[2-(5-Bromo-2-chloro-pyridin-4-yl)-1-hydroxy-1-methyl-ethyl]-piperidine-1-carboxylic acid tert-butyl ester

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent

Procedure

A solution of 4-[2-(5-bromo-2-chloro-pyridin-4-yl)-acetyl]-piperidine-1-carboxylic acid tert-butyl ester (9.80 g) in tetrahydrofuran (6 mL) is added dropwise to an ice cooled solution of methyl magnesium bromide (1.4 M in toluene/tetrahydrofuran 75:25, 74 mL). The reaction mixture is stirred for 30 min in the cooling bath and then at room temperature for 1 h. The mixture is poured into aqueous NH4Cl solution and extracted with ethyl acetate. The combined extracts are dried over MgSO4 and concentrated in vacuo. Since the residue still contains a considerable amount of starting material, it is azeotropically dried using toluene and resubmitted to the procedure described above. The crude product is purified by preparative HPLC (column: Waters X-Bridge C18; mobile phase: water+0.125% NH4OH/methanol 90:10→100:0) to give the title compound. LC (method 4): tR=1.33 min; Mass spectrum (ESI+): m/z=433, 435 [M+H]+.

Workup

  1. waitat room temperature for 1 h
  2. extractionextracted with ethyl acetate
  3. dry with materialThe combined extracts are dried over MgSO4
  4. concentrationconcentrated in vacuo
  5. customis azeotropically dried
  6. customThe crude product is purified by preparative HPLC (column: Waters X-Bridge C18; mobile phase: water+0.125% NH4OH/methanol 90:10→100:0)

Sources & evidence

ORD record
ord-cbe99897cf20473c8bd53997e55f403a
Source dataset
uspto-grants-2014_10
Patent number
US08853239B2

Reaction notes

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