Piperidine → 2,2-Difluoro-1-(piperidin-1-yl)-3-(4-(4,4,4-trifluorobutoxy)phenyl)propane-1,3-dione

HRID 1629788Notes

Reaction equation

HRID 1629788 reaction equation
[NH:1]1[CH2:6][CH2:5][CH2:4][CH2:3][CH2:2]1.[F:7][C:8]([F:29])([C:13](=[O:28])[C:14]1[CH:19]=[CH:18][C:17]([O:20][CH2:21][CH2:22][CH2:23][C:24]([F:27])([F:26])[F:25])=[CH:16][CH:15]=1)[C:9](OC)=[O:10]>C(Cl)Cl>[F:7][C:8]([F:29])([C:13]([C:14]1[CH:15]=[CH:16][C:17]([O:20][CH2:21][CH2:22][CH2:23][C:24]([F:25])([F:27])[F:26])=[CH:18][CH:19]=1)=[O:28])[C:9]([N:1]1[CH2:6][CH2:5][CH2:4][CH2:3][CH2:2]1)=[O:10]

Participants

4

Reactant 2

HCID 8082PiperidineHCID 86685881Methyl 2,2-difluoro-3-oxo-3-(4-(4,4,4-trifluorobutoxy)phenyl)propanoate

Product 1

HCID 866858802,2-Difluoro-1-(piperidin-1-yl)-3-(4-(4,4,4-trifluorobutoxy)phenyl)propane-1,3-dioneYield 89.9%

Reagents, catalysts & solvents 1

HCID 6344DichloromethaneSolvent

Procedure

Piperidine (175 μL, 1.763 mmol) was slowly added to Intermediate 103A (500 mg, 1.470 mmol) at rt. The reaction was stirred at rt for 3 h. The reaction was diluted with CH2Cl2, loaded onto a 12 g SiO2 column and eluted with EtOAc in hexanes. Fractions containing the product were combined and evaporated to dryness to provide the product (520 mg, 81%) as a clear oil. LCMS Anal. Calc'd for C18H20F5NO3 393.14, found [M+H] 394.2. 1H NMR (500 MHz, CDCl3) δ 8.10 (d, J=9.1 Hz, 2H), 6.98-6.91 (m, 2H), 4.10 (t, J=5.9 Hz, 2H), 3.61-3.56 (m, 2H), 3.54-3.50 (m, 2H), 2.39-2.26 (m, 2H), 2.14-2.05 (m, 2H), 1.69-1.61 (m, 2H), 1.60-1.51 (m, 4H).

Workup

  1. washeluted with EtOAc in hexanes
  2. additionFractions containing the product
  3. customevaporated to dryness

Sources & evidence

ORD record
ord-09993a06c38844ec9989329c736305a1
Source dataset
uspto-grants-2014_07
Patent number
US08791091B2

Reaction notes

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