2-Methylpiperidine → 5-Bromo-2-(2-methylpiperidin-1-YL)benzaldehyde

HRID 400748

Reaction equation

HRID 400748 reaction equation
[Br:1][C:2]1[CH:3]=[CH:4][C:5](F)=[C:6]([CH:9]=1)[CH:7]=[O:8].[CH3:11][CH:12]1[CH2:17][CH2:16][CH2:15][CH2:14][NH:13]1.C(=O)([O-])[O-].[Na+].[Na+]>CS(C)=O.O>[Br:1][C:2]1[CH:3]=[CH:4][C:5]([N:13]2[CH2:14][CH2:15][CH2:16][CH2:17][CH:12]2[CH3:11])=[C:6]([CH:9]=1)[CH:7]=[O:8]

Participants

6

Reactant 3

HCID 79742-MethylpiperidineHCID 10340Sodium CarbonateHCID 7363275-Bromo-2-fluorobenzaldehyde

Product 1

HCID 230911015-Bromo-2-(2-methylpiperidin-1-YL)benzaldehydeYield 89%

Reagents, catalysts & solvents 2

HCID 679Dimethyl SulfoxideSolventHCID 962WaterSolvent

Conditions

Temperature
120 °C

Procedure

To a solution of 5-bromo-2-fluorobenzaldehyde (13.20 g; 65.02 mmol) in DMSO (160 mL) and water (40 mL) were added 2-methylpiperidine (15.35 mL; 130.04 mmol) and anhydrous sodium carbonate (13.78 g; 130.04 mmol). The resulting mixture was heated at 120° C. for 16 h after which it was allowed to cool to RT. Reaction mixture was partitioned between H2O and Et2O and the combined organic layers were washed with brine (pH 5-6 adjusted with HCl), dried over MgSO4, filtered and dried under vacuum to give the title compound as a brown yellow oil (16.3 g, 89%). 1H NMR (CDCl3, 300 MHz) δ 10.40 (s, 1H), 7.93 (d, J=2.5 Hz, 1H), 7.62 (dd, J=8.6, 2.5 Hz, 1H), 7.12 (d, J=8.6 Hz, 1H), 3.17 (m, 1H), 3.06 (m, 1H), 2.81 (ddd, J=11.7, 7.6, 3.9 Hz, 1H), 1.89 (m, 1H), 1.83-1.65 (m, 3H), 1.58-1.42 (m, 2H), 0.91 (d, J=6.3 Hz, 3H). HPLC (Method A): Rt 2.20 min (Purity: 93.7%). LC/MS (Method B): 282.1 (M+H)+.

Workup

  1. temperatureto cool to RT
  2. customReaction mixture
  3. customwas partitioned between H2O and Et2O
  4. washthe combined organic layers were washed with brine (pH 5-6 adjusted with HCl)
  5. dry with materialdried over MgSO4
  6. filtrationfiltered
  7. customdried under vacuum

Sources & evidence

ORD record
ord-584d430c237c42bb943403b23a66ecda
Source dataset
uspto-grants-2014_06
Patent number
US08741923B2

Linked notes

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