Ammonium Chloride → HCID 86672761, compound

HRID 1754910Notes

Reaction equation

HRID 1754910 reaction equation
[F:1][C:2]([F:16])([O:6][C:7]1[CH:15]=[CH:14][C:10]([C:11]([OH:13])=O)=[CH:9][CH:8]=1)[CH:3]([F:5])[F:4].[C:17]([O:21][C:22]([N:24]1[CH2:29][CH2:28][C:27]([NH2:32])([C:30]#[N:31])[CH2:26][CH2:25]1)=[O:23])([CH3:20])([CH3:19])[CH3:18].C(N(CC)C(C)C)(C)C.[Cl-].[NH4+]>CN(C=O)C>[C:17]([O:21][C:22]([N:24]1[CH2:25][CH2:26][C:27]([C:30]#[N:31])([NH:32][C:11](=[O:13])[C:10]2[CH:9]=[CH:8][C:7]([O:6][C:2]([F:1])([F:16])[CH:3]([F:4])[F:5])=[CH:15][CH:14]=2)[CH2:28][CH2:29]1)=[O:23])([CH3:20])([CH3:18])[CH3:19]

Participants

6

Reactant 4

HCID 25517Ammonium ChlorideHCID 81531DiisopropylethylamineHCID 27766394-(1,1,2,2-Tetrafluoroethoxy)benzoic acidHCID 22091429tert-Butyl 4-amino-4-cyanopiperidine-1-carboxylate

Product 1

HCID 86672761HCID 86672761, compoundYield 86%

Reagents, catalysts & solvents 1

HCID 6228DimethylformamideSolvent

Procedure

N,N,N′,N′-Tetramethyl-O-(7-azabenzotriazol-1-yl)uoronium hexafluorophosphate (1.60 g, 4.20 mmol) was added to a solution of 4-(1,1,2,2-tetrafluoro-ethoxy)-benzoic acid (1.00 g, 4.20 mmol), 4-amino-4-cyano-piperidine-1-carboxylic acid tert-butyl ester (995 mg, 4.42 mmol) and N,N-diisopropylethylamine (1.46 ml, 8.39 mmol) in DMF (8.8 ml) at 0° C. The mixture was gradually warmed to room temperature and stirred for 28.5 hours. An aqueous ammonium chloride solution was added to the reaction mixture, followed by extraction with ethyl acetate three times. The organic layers were sequentially washed with H2O (×2) and saturated brine, and then dried over Na2SO4 and concentrated under reduced pressure. The residue was purified by column chromatography (hexane:AcOEt=90:10→30:70) to give 4-cyano-4-[4-(1,1,2,2-tetrafluoro-ethoxy)-benzoylamino]-piperidine-1-carboxylic acid tert-butyl ester as a light brown powder (1.60 g, 86%).

Workup

  1. extractionfollowed by extraction with ethyl acetate three times
  2. washThe organic layers were sequentially washed with H2O (×2) and saturated brine
  3. dry with materialdried over Na2SO4
  4. concentrationconcentrated under reduced pressure
  5. customThe residue was purified by column chromatography (hexane:AcOEt=90:10→30:70)

Sources & evidence

ORD record
ord-1201384aa0684e1a9a0869406b570194
Source dataset
uspto-grants-2015_10
Patent number
US09169254B2

Reaction notes

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