Trifluoroacetic acid → HCID 86721871, compound

HRID 1049014Notes

Reaction equation

HRID 1049014 reaction equation
C(OC([N:8]1[CH2:13][CH2:12][CH:11]([O:14][C:15]2[CH:20]=[CH:19][C:18]([S:21](=[O:35])(=[O:34])[N:22]([CH:30]3[CH2:33][CH2:32][CH2:31]3)[C:23]3[CH:28]=[CH:27][CH:26]=[C:25]([F:29])[CH:24]=3)=[CH:17][CH:16]=2)[CH2:10][CH2:9]1)=O)(C)(C)C.C(O)(C(F)(F)F)=O>C(Cl)Cl>[CH:30]1([N:22]([C:23]2[CH:28]=[CH:27][CH:26]=[C:25]([F:29])[CH:24]=2)[S:21]([C:18]2[CH:19]=[CH:20][C:15]([O:14][CH:11]3[CH2:10][CH2:9][NH:8][CH2:13][CH2:12]3)=[CH:16][CH:17]=2)(=[O:35])=[O:34])[CH2:33][CH2:32][CH2:31]1

Participants

4

Reactant 2

HCID 6422Trifluoroacetic acidHCID 86721870HCID 86721870, compound

Product 1

HCID 86721871HCID 86721871, compoundYield 73.7%

Reagents, catalysts & solvents 1

HCID 6344DichloromethaneSolvent

Procedure

To a solution of 4-{4-[cyclobutyl-(3-fluoro-phenyl)-sulfamoyl]-phenoxy}-piperidine-1-carboxylic acid tert-butyl ester (330 mg, 655 μmol) in DCM (9 mL) was added TFA (1 mL) and then the reaction was stirred at room temperature for 30 minutes. The reaction was concentrated and then purified by SCX eluting with 2 M NH3 in MeOH to give N-cyclobutyl-N-(3-fluoro-phenyl)-4-(piperidin-4-yloxy)-benzenesulfonamide (195 mg, 483 μmol). To a solution of N-cyclobutyl-N-(3-fluoro-phenyl)-4-(piperidin-4-yloxy)-benzenesulfonamide in DCM (10 mL) was added DIPEA (168 μL, 965 μmol) and methanesulfonyl chloride (41 μL, 531 μmol) and the reaction was stirred at room temperature for 30 minutes. Water was added and then extracted with DCM, filtered through a phase separator and concentrated. Purification by silica gel column chromatography (0-50% EtOAc in cyclohexane) followed by preparative reverse a phase HPLC gave the title compound (169 mg). 1H NMR δ (DMSO): 7.46 (2H, d, J=8.8 Hz), 7.38-7.39 (1H, m), 7.16-7.17 (3H, m), 6.77-6.78 (2H, m), 4.69-4.71 (1H, m), 4.20-4.22 (1H, m), 3.33-3.38 (4H, m), 3.13 (2H, ddd, J=12.1, 8.09, 3.4 Hz), 2.91 (3H, s), 2.03-2.06 (4H, m), 1.77-1.81 (4H, m), 1.53-1.56 (2H, m). LCMS (m/z, Method B) ES+ 482.9 [M+1]+.

Workup

  1. concentrationThe reaction was concentrated
  2. custompurified by SCX
  3. washeluting with 2 M NH3 in MeOH

Sources & evidence

ORD record
ord-e797d7965a7245c88e7b413e8f386f18
Source dataset
uspto-grants-2016_07
Patent number
US09382222B2

Reaction notes

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