Methyl iodide → 4-[(2-Bromo-phenyl)-methyl-amino]-piperidine-1-carboxylic acid tert-butyl ester

HRID 1093545Notes

Reaction equation

HRID 1093545 reaction equation
[C:1]([O:5][C:6]([N:8]1[CH2:13][CH2:12][CH:11]([NH:14][C:15]2[CH:20]=[CH:19][CH:18]=[CH:17][C:16]=2[Br:21])[CH2:10][CH2:9]1)=[O:7])([CH3:4])([CH3:3])[CH3:2].[H-].[Na+].[CH3:24]I>CN(C=O)C>[C:1]([O:5][C:6]([N:8]1[CH2:13][CH2:12][CH:11]([N:14]([C:15]2[CH:20]=[CH:19][CH:18]=[CH:17][C:16]=2[Br:21])[CH3:24])[CH2:10][CH2:9]1)=[O:7])([CH3:4])([CH3:2])[CH3:3]

Participants

5

Reactant 3

HCID 6328Methyl iodideHCID 24758Sodium hydrideHCID 43652150tert-Butyl 4-((2-bromophenyl)amino)piperidine-1-carboxylate

Product 1

HCID 665914084-[(2-Bromo-phenyl)-methyl-amino]-piperidine-1-carboxylic acid tert-butyl esterYield 45%

Reagents, catalysts & solvents 1

HCID 6228DimethylformamideSolvent

Procedure

To a solution of 4-(2-bromophenylamino)-piperidine-1-carboxylic acid tert-butyl ester (2.0 g, 0.00562 mole), in DMF (10 mL) was added NaH (60% w/w dispersion in oil) (0.9 g, 0.02251 mole) and the resulting mixture was stirred at ambient temperature for 10 minutes under an atmosphere of nitrogen. Methyl iodide (3.19 g, 0.0225 mole) was then added and stirring was continued for 30 minutes at ambient temperature. The reaction mixture was quenched with aqueous NH4Cl solution and the product was extracted with ether. The ether layer with washed with aqueous NaHCO3 solution followed by brine solution. The ether layer collected was dried over sodium sulfate and concentrated under reduced pressure. The resulting residue was washed with ether and dried to afford 0.893 g (45%) of 4-[(2-bromo-phenyl)-methyl-amino]-piperidine-1-carboxylic acid tert-butyl ester. 1H NMR (CDCl3): δ 7.6-7.54 (m, 1H), 7.28-7.2 (m, 1H), 7.14-7.08 (m, 1H), 6.96-6.88 (m, 1H), 4.2-4.0 (m, 2H), 3.3-3.2 (m, 1H), 2.8-2.7 (m, 2H), 2.7 (s, 3H), 1.7-1.6 (m, 2H), 1.6 (m, 1H), 1.45 (s, 9H). A solution of 4-[(2-bromo-phenyl)-methyl-amino]-piperidine-1-carboxylic acid tert-butyl ester (0.89 g, 0.0024 mole) in dioxane.HCl was stirred for 30 minutes. The reaction was concentrated under reduced pressure to afford 0.704 g (95%) of (2-bromo-phenyl)-methyl-piperidin-4-yl-amine. 1H NMR (DMSO-d6): δ 9.0 (bd, 3H), 7.6 (m, 1H), 7.4 (m, 2H), 7.0 (m, 1H), 3.2 (m, 3H), 2.9 (m, 2H), 2.6 (s, 3H), 1.9 (m, 3H).

Workup

  1. stirringstirring
  2. waitwas continued for 30 minutes at ambient temperature
  3. customThe reaction mixture was quenched with aqueous NH4Cl solution
  4. extractionthe product was extracted with ether
  5. washThe ether layer with washed with aqueous NaHCO3 solution
  6. customThe ether layer collected
  7. dry with materialwas dried over sodium sulfate
  8. concentrationconcentrated under reduced pressure
  9. washThe resulting residue was washed with ether
  10. customdried

Sources & evidence

ORD record
ord-ec53e2eec5f0420b89e15c632aaa90b8
Source dataset
uspto-grants-2012_03
Patent number
US08129376B2

Reaction notes

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