18-Crown-6 → 3-[(6-Chloro-2-fluoro-3-methylphenyl)oxy]-5-fluorobenzonitrile

HRID 1875227Notes

Reaction equation

CC([O-])(C)C.[K+].[Cl:7][C:8]1[C:13]([OH:14])=[C:12]([F:15])[C:11]([CH3:16])=[CH:10][CH:9]=1.C1OCCOCCOCCOCCOCCOC1.[F:35][C:36]1[CH:37]=[C:38]([CH:41]=[C:42](F)[CH:43]=1)[C:39]#[N:40]>C1COCC1.CS(C)=O.O>[Cl:7][C:8]1[C:13]([O:14][C:42]2[CH:41]=[C:38]([CH:37]=[C:36]([F:35])[CH:43]=2)[C:39]#[N:40])=[C:12]([F:15])[C:11]([CH3:16])=[CH:10][CH:9]=1

Participants

Conditions

Temperature: 120 °C

Procedure

KOtBu (6.23 ml of a 1M solution in THF, 6.23 mmol) was added to a solution of 6-chloro-2-fluoro-3-methylphenol (1.00 g, 6.23 mmol) and 18-CROWN-6 (0.823 g, 3.11 mmol) in DMSO (12 ml) at RT. After 20 mins, 3,5-difluorobenzonitrile (0.87 g, 6.23 mmol) was added and the solution was heated at 120° C. overnight. The reaction mixture was poured into water (50 mL) and extracted with EtOAc (2×20 mL). The organic layer was dried (Na2SO4), filtered, concentrated, and purified by silica gel chromatography (0-25% EtOAc/hexs) to provide 3-[(6-chloro-2-fluoro-3-methylphenyl)oxy]-5-fluorobenzonitrile (1.15 g, 66%) as an off-white solid. 1H NMR (400 MHz, CHLOROFORM-d) δ ppm 7.21 (dd, J=8.42, 1.46 Hz, 1H), 7.06-7.14 (m, 2H), 6.87-6.95 (m, 2H), 2.33 (d, J=2.11 Hz, 3H).

Workup

extractionextracted with EtOAc (2×20 mL)
dry with materialThe organic layer was dried (Na2SO4)
filtrationfiltered
concentrationconcentrated
custompurified by silica gel chromatography (0-25% EtOAc/hexs)

Sources & evidence

ORD record: ord-488601bbd8224f1abe12fafb9e04a61d
Source dataset: uspto-grants-2012_11
DOI: 10.6084/m9.figshare.5104873.v1
Patent number: US08304419B2

Reaction notes

Loading…