Water → N-[2-(2,4-Dichlorophenoxy)phenyl]piperidin-4-amine

HRID 1642233Notes

Reaction equation

FC(F)(F)C(O)=O.C(OC([N:15]1[CH2:20][CH2:19][CH:18]([NH:21][C:22]2[CH:27]=[CH:26][CH:25]=[CH:24][C:23]=2[O:28][C:29]2[CH:34]=[CH:33][C:32]([Cl:35])=[CH:31][C:30]=2[Cl:36])[CH2:17][CH2:16]1)=O)(C)(C)C.C([O-])([O-])=O.[K+].[K+].O>C(Cl)Cl>[Cl:36][C:30]1[CH:31]=[C:32]([Cl:35])[CH:33]=[CH:34][C:29]=1[O:28][C:23]1[CH:24]=[CH:25][CH:26]=[CH:27][C:22]=1[NH:21][CH:18]1[CH2:19][CH2:20][NH:15][CH2:16][CH2:17]1

Participants

Conditions

Temperature: 0 °C

Procedure

Trifluoroacetic acid (TFA, 3 mL) was added to a solution of 4-[2-(2,4-dichlorophenoxy)phenylamino]piperidine-1-carboxylic acid tert-butyl ester (AMR01030, 300 mg, 0.686 mmol) in dry DCM (6 mL) at 0° C. After stirring at 0° C. for 30 min, the mixture was poured into solid K2CO3 (8.4 g) and water (33 mL) was added. The solution was extracted with DCM (3×20 mL) and the organic layer was dried (MgSO4), filtered and evaporated to give [2-(2,4-dichlorophenoxy)phenyl]piperidin-4-ylamine (225 mg, 97%) as an oil which was used in the next step without further purification. Rf: 0.13 (DCM/methanol 4:1 plus 3 drops of triethylamine) 1H NMR (270 MHz, CDCl3) δ 1.27 (2H, m, CH2), 1.84 (1H, br s, NH), 2.02 (2H, d, J=12.9 Hz, CH2), 2.72 (2H, t, J=11.9 Hz, CH2), 3.06 (2H, br d, J=12.6 Hz, CH2), 3.39 (1H, m, NH), 4.04 (1H, d, J=6.8 Hz, CH), 6.59 (1H, m, ArH), 6.77 (2H, m, ArH), 7.01 (1H, m, ArH), 7.10 (1H, m, ArH) and 7.42 (1H, m, ArH).

Workup

additionwas added
extractionThe solution was extracted with DCM (3×20 mL)
dry with materialthe organic layer was dried (MgSO4)
filtrationfiltered
customevaporated

Sources & evidence

ORD record: ord-5429fc63f8c2439390c3653272e7902f
Source dataset: uspto-grants-2012_02
DOI: 10.6084/m9.figshare.5104873.v1
Patent number: US08119627B2

Reaction notes

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