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

HRID 1093548Notes

Reaction equation

HRID 1093548 reaction equation
C(OC([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[Cl:21])[CH2:10][CH2:9]1)=O)(C)(C)C.Cl.O1CCOC[CH2:24]1>>[ClH:21].[Cl:21][C:16]1[CH:17]=[CH:18][CH:19]=[CH:20][C:15]=1[N:14]([CH3:24])[CH:11]1[CH2:10][CH2:9][NH:8][CH2:13][CH2:12]1

Participants

4

Reactant 3

HCID 313Hydrochloric AcidHCID 312751,4-DioxaneHCID 22557784tert-Butyl 4-(2-chloroanilino)piperidine-1-carboxylate

Product 1

HCID 66591723(2-Chloro-phenyl)-methyl-piperidin-4-yl-amine hydrochlorideYield 99%

Procedure

To a solution of 4-(2-chloro-phenylamino)-piperidine-1-carboxylic acid tert-butyl ester (0.166 g, 0.00053 mole), in DMF (10 mL) was added, NaH (60% w/w dispersion in oil) (0.0512 g, 0.0021 mole) and the resulting mixture was stirred at ambient temperature for 10 minutes under an atmosphere of nitrogen. Methyl iodide (0.303 g, 0.0021 mole) was then added, and the stirring was continued for 30 minutes at ambient temperature. The reaction mixture was heated to 45° C. for 30 minutes. The reaction mixture was then quenched with aqueous 10% NH4Cl solution and the product was extracted with ethyl acetate. The ethyl acetate layer was washed with aqueous NaHCO3 solution followed by brine solution. The organic layer was collected, dried over sodium sulfate and concentrated under reduced pressure to afford 0.08 g (46%) of 4-[(2-chloro-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-chloro-phenylamino)-piperidine-1-carboxylic acid tert-butyl ester (0.078 g, 0.00024 mole) in dioxane.HCl (1 mL) was stirred for 30 minutes. The reaction mixture was then concentrated under reduced pressure to afford 0.072 g (99%) of (2-chloro-phenyl)-methyl-piperidin-4-yl-amine hydrochloride which was used in the next step without further purification.

Workup

  1. concentrationThe reaction mixture was then concentrated under reduced pressure

Sources & evidence

ORD record
ord-4200d35d9cce40b4b03b4a99d1816654
Source dataset
uspto-grants-2012_03
Patent number
US08129376B2

Reaction notes

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