Hydrochloric Acid → (2-Bromo-phenyl)-methyl-piperidin-4-yl-amine

HRID 1093546Notes

Reaction equation

HRID 1093546 reaction equation
C(OC([N:8]1[CH2:13][CH2:12][CH:11]([N:14]([C:16]2[CH:21]=[CH:20][CH:19]=[CH:18][C:17]=2[Br:22])[CH3:15])[CH2:10][CH2:9]1)=O)(C)(C)C.Cl>O1CCOCC1>[Br:22][C:17]1[CH:18]=[CH:19][CH:20]=[CH:21][C:16]=1[N:14]([CH3:15])[CH:11]1[CH2:12][CH2:13][NH:8][CH2:9][CH2:10]1

Participants

4

Reactant 2

HCID 313Hydrochloric AcidHCID 665914084-[(2-Bromo-phenyl)-methyl-amino]-piperidine-1-carboxylic acid tert-butyl ester

Product 1

HCID 57874448(2-Bromo-phenyl)-methyl-piperidin-4-yl-amineYield 109%

Reagents, catalysts & solvents 1

HCID 312751,4-DioxaneSolvent

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. concentrationThe reaction was concentrated under reduced pressure

Sources & evidence

ORD record
ord-043692e8c0fc4998a506cfd15e0146e0
Source dataset
uspto-grants-2012_03
Patent number
US08129376B2

Reaction notes

Loading…