Ethyl Acetate → 4-[1-(2,5-Difluoro-4-methanesulfinyl-phenyl)-piperidin-4-ylideneaminooxy]-piperidine-1-carboxylic acid isopropyl ester

HRID 2066855Notes

Reaction equation

HRID 2066855 reaction equation
[NH:1]1[CH2:6][CH2:5][C:4](=[N:7][O:8][CH:9]2[CH2:14][CH2:13][N:12]([C:15]([O:17][CH:18]([CH3:20])[CH3:19])=[O:16])[CH2:11][CH2:10]2)[CH2:3][CH2:2]1.[F:21][C:22]1[CH:27]=[C:26]([S:28]([CH3:30])=[O:29])[C:25]([F:31])=[CH:24][C:23]=1F.C(N(C(C)C)CC)(C)C.C(OCC)(=O)C>CS(C)=O>[CH:18]([O:17][C:15]([N:12]1[CH2:11][CH2:10][CH:9]([O:8][N:7]=[C:4]2[CH2:3][CH2:2][N:1]([C:23]3[CH:24]=[C:25]([F:31])[C:26]([S:28]([CH3:30])=[O:29])=[CH:27][C:22]=3[F:21])[CH2:6][CH2:5]2)[CH2:14][CH2:13]1)=[O:16])([CH3:20])[CH3:19]

Participants

6

Reactant 4

HCID 8857Ethyl AcetateHCID 81531DiisopropylethylamineHCID 57461147Isopropyl 4-(Piperidin-4-ylideneaminooxy)piperidine-1-carboxylateHCID 673085031,2,4-Trifluoro-5-methanesulfinyl-benzene

Product 1

HCID 583335694-[1-(2,5-Difluoro-4-methanesulfinyl-phenyl)-piperidin-4-ylideneaminooxy]-piperidine-1-carboxylic acid isopropyl ester

Reagents, catalysts & solvents 1

HCID 679Dimethyl SulfoxideSolvent

Conditions

Temperature
120 °C

Procedure

2d (0.78 g, 1.76 mmol) and 43b (0.66 g, 3.39 mmol) were combined with diisopropylethylamine (0.91 mL, 5.5 mmol) in DMSO (8 mL) and heated to 120° C. overnight. The mixture was cooled to room temperature and poured into 20 mL of ethyl acetate, washed with water (20 mL) and brine (3×20 mL), dried and concentrated. The residue was purified by flash chromatography (eluent: 50 to 90% of EtOAc+0.1% triethylamine in hexane) to afford 4-[1-(2,5-difluoro-4-methanesulfinyl-phenyl)-piperidin-4-ylideneaminooxy]-piperidine-1-carboxylic acid isopropyl ester 43-1. This material was recrystallized from toluene and hexane to afford 43-1 as a white powder: HPLC, LC-MS 458.1 (MH), tR=6.98 (Method 2). EC50: 58 nM.

Workup

  1. temperatureThe mixture was cooled to room temperature
  2. washwashed with water (20 mL) and brine (3×20 mL)
  3. customdried
  4. concentrationconcentrated
  5. customThe residue was purified by flash chromatography (eluent: 50 to 90% of EtOAc+0.1% triethylamine in hexane)

Sources & evidence

ORD record
ord-f3ab06a13ed442e3b12ce3487ab0829f
Source dataset
uspto-grants-2012_10
Patent number
US08293729B2

Reaction notes

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