Sodium Hydroxide → 6-Chloro-2-(2,2-difluoro-ethoxy)-nicotinonitrile

HRID 1664429Notes

Reaction equation

O=P(Cl)(Cl)Cl.[Cl:6][C:7]1[CH:15]=[CH:14][C:10]([C:11]([NH2:13])=O)=[C:9]([O:16][CH2:17][CH:18]([F:20])[F:19])[N:8]=1.[OH-].[Na+]>C(#N)C>[Cl:6][C:7]1[CH:15]=[CH:14][C:10]([C:11]#[N:13])=[C:9]([O:16][CH2:17][CH:18]([F:19])[F:20])[N:8]=1

Participants

Conditions

Temperature: 60 °C

Procedure

POCl3 (7.5 mL, 81 mmol) was added to a solution of 6-chloro-2-(2,2-difluoro-ethoxy)-nicotinamide (6.39 g, 27.0 mmol) in acetonitrile (100 mL) at 14° C. over 5 minutes. The reaction mixture was heated to 60° C. for 1.5 hours then cooled to room temperature. The mixture was poured into an ice cold solution of aqueous NaOH (0.6M, 800 mL) and extracted with EtOAc (4×800 mL). The organic extracts were combined, dried over Na2SO4, filtered and concentrated. The residue was purified by silica gel flash column chromatography (20% ethyl acetate/hexanes) to give the title compound as a light yellow oil which solidified upon standing (5.10 g, 86%).

Workup

temperaturethen cooled to room temperature
extractionextracted with EtOAc (4×800 mL)
dry with materialdried over Na2SO4
filtrationfiltered
concentrationconcentrated
customThe residue was purified by silica gel flash column chromatography (20% ethyl acetate/hexanes)

Sources & evidence

ORD record: ord-5ab87c13b12d4580b321455a3e13c480
Source dataset: uspto-grants-2011_10
DOI: 10.6084/m9.figshare.5104873.v1
Patent number: US08039450B2

Reaction notes

Loading…