Water → 2-(2,4-Dichlorophenoxy)-N-(piperidin-4-yl)benzamide

HRID 1642244Notes

Reaction equation

HRID 1642244 reaction equation
FC(F)(F)C(O)=O.C(OC([N:15]1[CH2:20][CH2:19][CH:18]([NH:21][C:22](=[O:38])[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[C:22]([NH:21][CH:18]1[CH2:19][CH2:20][NH:15][CH2:16][CH2:17]1)=[O:38]

Participants

6

Reactant 4

HCID 962WaterHCID 6422Trifluoroacetic acidHCID 11430Potassium CarbonateHCID 15952164HCID 15952164, compound

Product 1

HCID 575503182-(2,4-Dichlorophenoxy)-N-(piperidin-4-yl)benzamideYield 100%

Reagents, catalysts & solvents 1

HCID 6344DichloromethaneSolvent

Conditions

Temperature
0 °C

Procedure

Trifluoroacetic acid (TFA, 9 mL) was added to a solution of 4-[2-(2,4-dichlorophenoxy)-benzoylamino]piperidine-1-carboxylic acid tert-butyl ester (AMR01070, 900 mg, 1.93 mmol) in dry DCM (20 mL) at 0° C. After stirring at 0° C. for 1 h, the mixture was poured into solid K2CO3 (2.5 g) and water (100 mL) was added. The solution was extracted with DCM (3×30 mL) and the organic layer was dried (MgSO4), filtered and evaporated to give 4-[2-(2,4-dichlorophenoxy)-N-piperidin-4-ylbenzamide (AMR01077, 705 mg, 100%) as a white solid, which was used in the next step without further purification. Rf: 0.25 (DCM/MeOH 9:1) 1H NMR (270 MHz, CDCl3) δ 1.87 (2H, m, CH2), 2.21 (2H, d, J=11.4 Hz, CH2), 3.01 (2H, q, J=10.9 Hz, CH2), 3.43 (2H, d, J=13.1 Hz, CH2), 4.22 (1H, m, CH), 6.76 (1H, dd, J=8.4, 1.0 Hz, ArH), 6.95 (1H, d, J=8.7 Hz, ArH), 7.21-7.27 (2H, m, ArH), 7.41 (1H, m, ArH), 7.51 (1H, d, J=2.5 Hz, ArH), 8.14 (1H, dd, J=7.9, 2.0 Hz, ArH), 9.25 (1H, br d, J=8.5 Hz, NH) and 9.56 (1H, br d, J=7.4 Hz, NH). 13C NMR (270 MHz, CDCl3) δ 28.61 (CH2), 43.11 (CH2), 44.90 (CH), 117.10, 123.43, 124.53, 126.40, 128.58, 130.83, 130.98, 132.53, 133.24, 149.35, 154.00 (ArC) and 164.38 (C═N).

Workup

  1. additionwas added
  2. extractionThe solution was extracted with DCM (3×30 mL)
  3. dry with materialthe organic layer was dried (MgSO4)
  4. filtrationfiltered
  5. customevaporated

Sources & evidence

ORD record
ord-8a98a215599544609b2269eadbacc1e3
Source dataset
uspto-grants-2012_02
Patent number
US08119627B2

Reaction notes

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