Fenarimol synthesis

Yield:60168-88-9 20%

Reaction Conditions:

Stage #1:2-bromo-1-chlorobenzene with magnesium;ethylene dibromide in tetrahydrofuran for 1.58333 h;
Stage #2:(4-chlorophenyl)(pyrimidin-5-yl)methanone with zinc(II) chloride in tetrahydrofuran at 20; for 0.5 h;

Steps:

3.3
To a suspension of magnesium turnings (1.00 g, excess) in THF (20 mL) was added 1,2-dibromoethane (0.05 mL). After 5 min, o-bromochlorobenzene (960 mg, 5 mmol) was added in one portion, causing slight warming as the oxidative addition initiated. After 90 min. a menthol-phenanthroline titration of this solution indicated 100% insertion. This grey solution was treated with ZnCl₂ (680 mg, 5 mmol) and then with 23 (1.1 g, 5 mmol). The resulting yellow-brown solution was stirred at rt for 30 min during which all of 23 was consumed according to TLC. The mixture was washed with NH₄C1, sat. aq. NaHC0₃, and the organic layer was evaporated under reduced pressure to a brown gum. This residue was subjected to chromatography over 15 g of silica gel, eluting with 3: 1 hexane-EtOAc going to 1: 1 hexane-EtOAc. Evaporation of the eluant between 100 mL and 250 mL afforded 19 as a white solid (330 mg, 20%). Mp = 115-116 °C; 1H NMR (300 MHz, CDC1₃) δ ppm 9.00 (s, 1H), 8.48 (s, 2H), 8.20-7.08 (m, 8H, Ar); ¹³C NMR (75 MHz, CDC1₃) δ 160.1, 156.7, 138.7, 138.1, 137.5, 132.8, 132.3, 128.9, 128.4,128.2, 127.4, 118.4, 118.5, 80.1.

References:

REGENTS OF THE UNIVERSITY OF MINNESOTA;VINCE, Robert;VARTAK, Ashish P. WO2012/128965, 2012, A2 Location in patent:Page/Page column 16-17

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