Ammonium Chloride → 1-(Bromomethyl)-4-(trifluoromethoxy)benzene

A suspension of zinc dust (15 g, excess) in THF (100 mL) was treated with LiCl (10.00 g, 238 mmol) and 1,2-dibromoethane (0.5 mL, catalytic). The warm mixture thus formed was treated dropwise with a solution of 4-(trifluoromethoxy)benzyl bromide (10a) (50.00 g, 209 mmol) in THF (200 mL) over a period of 3 hours. The resulting mixture was stirred for an additional hour, affording a solution of the lithium zincate 11, and then treated with (Ph3P)2NiCl2 (300 mg, 0.1 mol or 0.001 equivalents). The red suspension was treated drop wise with a solution of 5-bromopyrimidine (4) (33.23 g, 200 mmol) in THF (50 mL) over a period of one hour. The mixture was stirred for another 10 minutes and then poured into 300 mL of saturated aq. NH4Cl. The aqueous layer was washed with 200 mL of THF-ether (1:1), the combined organic layers washed with saturated aqueous NaHCO3, filtered, dried (MgSO4) and evaporated under reduced pressure to afford a pale yellow oily residue weighing 51.00 g (96%) and was found to be pure 5-[4-(trifluoromethoxy)benzyl]pyrimidine (12). 1H NMR (400 MHz, CDCl3) δ ppm 9.26 (s, 1H, pyrimidine), 8.84 (s, 2H, pyrimidine), 7.19 (s, 4H, Ar, no para-pattern observed), 4.06 (s, 2H, methylene); 13C NMR (100 MHz, CDCl3) 156.3, 157.1, 147.4, 139.6, 134.8, 131, 121.7, 35.0. ESI-MS (low-res) 255.0 (M+H)+.

1. washThe aqueous layer was washed with 200 mL of THF-ether (1:1)
2. washthe combined organic layers washed with saturated aqueous NaHCO3
3. filtrationfiltered
4. dry with materialdried (MgSO4)
5. customevaporated under reduced pressure
6. customto afford a pale yellow oily residue

ORD record

ord-c76a22b2a0f94194af770536ba4b885b

Source dataset

uspto-grants-2015_10

DOI

10.6084/m9.figshare.5104873.v1

Patent number

US09169216B2