Pyridine → 1-(3-(5,6-Dichloro-3-cyanopyridin-2-yloxy)propyl)cyclopropyl 2,2,2-trifluoroacetate

HRID 1020815Notes

Reaction equation

HRID 1020815 reaction equation
[F:1][C:2]([F:25])([F:24])[C:3]([O:5][C:6]1([CH2:9][CH2:10][CH2:11][O:12][C:13]2[C:18]([C:19](=O)[NH2:20])=[CH:17][C:16]([Cl:22])=[C:15]([Cl:23])[N:14]=2)[CH2:8][CH2:7]1)=[O:4].O=P(Cl)(Cl)Cl.N1C=CC=CC=1>CC#N.[OH-].[Na+]>[F:24][C:2]([F:1])([F:25])[C:3]([O:5][C:6]1([CH2:9][CH2:10][CH2:11][O:12][C:13]2[C:18]([C:19]#[N:20])=[CH:17][C:16]([Cl:22])=[C:15]([Cl:23])[N:14]=2)[CH2:8][CH2:7]1)=[O:4]

Participants

6

Reactant 3

HCID 1049PyridineHCID 24813Phosphorus oxychlorideHCID 866617241-(3-(3-Carbamoyl-5,6-dichloropyridin-2-yloxy)propyl)cyclopropyl 2,2,2-trifluoroacetate

Product 1

HCID 866617251-(3-(5,6-Dichloro-3-cyanopyridin-2-yloxy)propyl)cyclopropyl 2,2,2-trifluoroacetateYield 97%

Reagents, catalysts & solvents 2

HCID 6342AcetonitrileSolventHCID 14798Sodium HydroxideSolvent

Procedure

To the crude 1-(3-(3-carbamoyl-5,6-dichloropyridin-2-yloxy)propyl)cyclopropyl 2,2,2-trifluoroacetate in MeCN (20 mL) was added POCl3 (700 mg, 4.6 mmol) and pyridine (720 mg, 9 mmol) at room temperature. After being stirred for 2 h at room temperature, the mixture was diluted with 30 mL of sodium hydroxide solution, then extracted with ethyl acetate (2×50 mL), the combined organic layers were washed with brine twice, dried over Na2SO4, concentrated and purified by column chromatography (silica gel, Petroleum ether:EtOAc=1:0 to 10:1) to give the product 1-(3-(5,6-dichloro-3-cyanopyridin-2-yloxy)propyl)cyclopropyl 2,2,2-trifluoroacetate (0.87 g, 97%). 1H-NMR (400 MHz, DMSO-d6) δ (ppm) 8.68 (s, 1H), 4.39 (t, 2H, J=6.4 Hz), 1.90 (m, 4H), 1.05 (t, 2H, J=6.8 Hz), 0.84 (t, 2H, J=6.8 Hz).

Workup

  1. extractionextracted with ethyl acetate (2×50 mL)
  2. washthe combined organic layers were washed with brine twice
  3. dry with materialdried over Na2SO4
  4. concentrationconcentrated
  5. custompurified by column chromatography (silica gel, Petroleum ether:EtOAc=1:0 to 10:1)

Sources & evidence

ORD record
ord-915b117133f44807958b46de44d59155
Source dataset
uspto-grants-2014_05
Patent number
US08716478B2

Reaction notes

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