Water → N-[2-(2,4-Dichlorophenoxy)phenyl]piperidine-4-carboxamide

HRID 1642231Notes

Reaction equation

FC(F)(F)C(O)=O.C(OC([N:15]1[CH2:20][CH2:19][CH:18]([C:21](=[O:38])[NH:22][C:23]2[CH:28]=[CH:27][CH:26]=[CH:25][C:24]=2[O:29][C:30]2[CH:35]=[CH:34][C:33]([Cl:36])=[CH:32][C:31]=2[Cl:37])[CH2:17][CH2:16]1)=O)(C)(C)C.C([O-])([O-])=O.[K+].[K+].O>C(Cl)Cl>[Cl:37][C:31]1[CH:32]=[C:33]([Cl:36])[CH:34]=[CH:35][C:30]=1[O:29][C:24]1[CH:25]=[CH:26][CH:27]=[CH:28][C:23]=1[NH:22][C:21]([CH:18]1[CH2:19][CH2:20][NH:15][CH2:16][CH2:17]1)=[O:38]

Participants

Conditions

Temperature: 0 °C

Procedure

AMR01036 Trifluoroacetic acid (TFA, 1 mL) was added to a solution of 4-[2-(2,4-dichlorophenoxy)-phenylcarbamoyl]piperidine-1-carboxylic acid tert-butyl ester (AMR01.032, 100 mg, 0.215 mmol) in dry DCM (2 mL) at 0° C. After stirring at 0° C. for 30 min, the mixture was poured into solid K2CO3 (2.8 g) and water (11 mL) was added. The solution was extracted with DCM (3×20 mL) and the organic layer was dried (MgSO4), filtered and evaporated to give piperidine-4-carboxylic acid [2-(2,4-dichlorophenoxy)phenyl]amide (61 mg, 90%) as an oil which was used in the next step without further purification. Rf: 0.175 (DCM/methanol 4:1 plus 3 drops of triethylamine) 1H NMR (270 MHz, CDCl3) δ 1.66 (2H, m, CH2), 1.87 (2H, m, CH2), 2.24 (1H, br s, NH), 2.40 (1H, tt, CH), 2.66 (2H, td, CH2), 3.15 (2H, br d, J=12.6 Hz, CH2), 6.72 (1H, dd, J=8.2, 1.5 Hz, ArH), 6.93 (1H, d, J=8.6 Hz, ArH), 6.99 (1H, td, J=7.9, 1.5 Hz, ArH), 7.12 (1H, td, J=7.9, 1.2 Hz, ArH), 7.20 (1H, dd, J=8.9, 2.5 Hz, ArH), 7.47 (1H, d, J=2.5 Hz, ArH) and 8.41 (1H, dd, J=7.9, 1.2 Hz, 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-c93af569be3842ddaeb35f20f9109a10
Source dataset: uspto-grants-2012_02
DOI: 10.6084/m9.figshare.5104873.v1
Patent number: US08119627B2

Reaction notes

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