4-Bromo-2-methoxypyrimidine synthesis

Yield: 17%

Reaction Conditions:

Stage #1:2-methoxypyrimidine with 2,2,6,6-tetramethyl-piperidine;isopropyl chloride;magnesium;lithium chloride in tetrahydrofuran at -60; for 1 h;
Stage #2: with bromine;zinc(II) chloride in tetrahydrofuran at 20; for 2 h;

Steps:

6 Example 6:
2-methoxypyrimidine (28 g, 0.26 mol) was dissolved in tetrahydrofuran (200 ml) at -60 °C.The prepared TMP.MgCl.LiCl solution was added dropwise, and after the addition was completed, the mixture was stirred for 1 hour.Anhydrous zinc chloride (39 g, 0.28 mol) was added, and the temperature was slowly raised to room temperature, and bromine (45 g, 0.28 mol) was added dropwise, after 2 hours.The reaction was quenched by adding 1 mol/L aqueous hydrochloric acid to pH 7.The aqueous layer was separated and extracted with ethyl acetate (200 ml * 3 times), and the organic layer was combined and dried.Purification by column chromatography (PE: EA = 10:1) gave 8.3 g (yield: 17%).
Preparation TMP.MgCl.LiCl: Magnesium (8 g, 0.33 mol) and anhydrous lithium chloride (15 g, 0.33 mol) were placed in a dry three-necked flask, and a solution of 2-chloropropane (28.5 g, 0.3 mol) in tetrahydrofuran (200 ml) was added.After the addition was completed, stir at room temperature for 2 hours.Add 2,2,6,6-tetramethylpiperidine (60 g. 0.36 mol), stir overnight, to obtain a brown solution TMP.MgCl.LiCl;

References:

Zhengzhou Taifeng Pharmaceutical Co., Ltd.;Sha Wei;Liu Yang;Li Ting CN109761908, 2019, A Location in patent:Paragraph 0010; 0020-0021