Sodium Hydroxide → HCID 58576452, compound

HRID 2355558Notes

Reaction equation

HRID 2355558 reaction equation
Cl[C:2]1[CH:7]=[CH:6][C:5]([C:8]([F:11])([F:10])[F:9])=[CH:4][N:3]=1.[C:12]([O:16][C:17]([N:19]1[CH2:24][CH2:23][CH:22]([NH2:25])[CH2:21][CH2:20]1)=[O:18])([CH3:15])([CH3:14])[CH3:13].[OH-].[Na+]>CC(N(C)C)=O>[C:12]([O:16][C:17]([N:19]1[CH2:24][CH2:23][CH:22]([NH:25][C:2]2[CH:7]=[CH:6][C:5]([C:8]([F:11])([F:10])[F:9])=[CH:4][N:3]=2)[CH2:21][CH2:20]1)=[O:18])([CH3:15])([CH3:13])[CH3:14]

Participants

5

Reactant 3

HCID 14798Sodium HydroxideHCID 923422-Chloro-5-(trifluoromethyl)pyridineHCID 12682914-Amino-1-Boc-piperidine

Product 1

HCID 58576452HCID 58576452, compoundYield 15%

Reagents, catalysts & solvents 1

HCID 31374DimethylacetamideSolvent

Procedure

A solution of 2-chloro-5-trifluoromethyl-pyridine (2.45 g, 13.50 mmol, 1.0 equiv; commercially available) and 4-amino-piperidine-1-carboxylic acid tert-butyl ester (3.24 g, 16.19 mmol, 1.2 equiv; commercially available) in DMAc (12 mL) was heated by microwave irradiation to 155° C. for 6 h. A solution of 1 M NaOH (100 mL) was added and the reaction mixture extracted with ethyl acetate (3×100 mL). The combined organic phases were dried over MgSO4, concentrated by evaporation under reduced pressure and the crude material purified with column chromatography on silica eluting with a gradient of heptane/ethyl acetate (4:1→1:1) to yield 0.69 g (15%) of the title compound. 1H NMR (300 MHz, CDCl3): δ1.31-1.47 (m, 2H), 1.40 (s, 9H), 1.92-1.98 (m, 2H), 2.81-2.92 (m, 2H), 3.72-3.83 (m, 1H), 3.97-4.03 (m, 2H), 4.77 (d, J=8.1 Hz, 1H), 6.31 (d, J=8.8 Hz, 1H), 7.62 (dd, J=8.8 Hz, J=2.2 Hz, 1H), 8.25 (br s, 1H). 13C NMR (75 MHz, CDCl3): δ27.45, 31.17, 41.64, 47.51, 78.72, 105.86, 114.65 (q, J=32.8 Hz), 123.58 (q, J=268.6 Hz), 133.26, 145.15, 153.76, 158.36. 19F NMR (282 MHz, CDCl3): 1-61.22. MS (ISP): 346.1 [M+H]+.

Workup

  1. extractionthe reaction mixture extracted with ethyl acetate (3×100 mL)
  2. dry with materialThe combined organic phases were dried over MgSO4
  3. concentrationconcentrated by evaporation under reduced pressure
  4. customthe crude material purified with column chromatography on silica eluting with a gradient of heptane/ethyl acetate (4:1→1:1)

Sources & evidence

ORD record
ord-7597b13c4d9d45d283ed252cb8d4b852
Source dataset
uspto-grants-2010_07
Patent number
US07754744B2

Reaction notes

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