ChemicalBook CAS DataBase List 5-bromo-2-(trifluoromethyl)pyrimidine

5-bromo-2-(trifluoromethyl)pyrimidine synthesis

4synthesis methods

Product Name:5-bromo-2-(trifluoromethyl)pyrimidine
CAS Number:799557-86-1
Molecular formula:C5H2BrF3N2
Molecular Weight:226.98

680-15-9 Synthesis

Methyl 2,2-difluoro-2-(fluorosulfonyl)acetate

680-15-9
246 suppliers
$13.00/5g

183438-24-6 Synthesis

183438-24-6
387 suppliers
$6.00/1g

799557-86-1
158 suppliers
$57.00/500mg

Yield:799557-86-1 76.6%

Reaction Conditions:

with copper(l) iodide in N,N-dimethyl-formamide at 80 - 90; for 3 h;

Steps:

1C.1

In step 1, DMF (149.6 kg, 7 L/kg compound 8A) was charged to an inerted reactor with stirring. Compound 8 A (22.5 kg, 78.98 moles, 1 equivalent) was charged to the reactor followed by Cul (6 kg, 0.4 eq., 2.674 kg/kg compound 8A) and followed by Me02CCF2S02F (21.2 kg, 0.944 kg/kg compound 8A). The reactor contents were stirred at 80- 90 °C for at least 3 hours to form a reaction product mixture comprising compound 8B. The reactor was sampled and tested for compound 8A content by LC with a limit of < 5% compound 8A. Mixing at 80-90 °C was continued until compound 8A content was < 5%. 25 molar NaHCCE (371.3 kg, 16.5 kg/kg compound 8A) was combined with the reaction product mixture and held for 6 hours with stirring at 20-30 °C. MTBE (116.6 kg, 5.18 kg/kg compound 8A) was combined with the reaction product mixture followed by celite filter aids (22.5 kg, 1 kg/kg compound 8A). The reaction product mixture was stirred for 15 minutes at 20-30 °C, filtered, and the filtrate was collected. The filter cake was washed with MTBE (33.3 kg, 1.48 kg/kg compound 8A) and the filtrates were combined.The collected filtrate was allowed to settle for at least 10 minutes and the bottom aqueous layer was removed. The aqueous layer was washed twice with MTBE (116.6 kg, 5.18 kg/kg compound 8A), where a phase separation and aqueous layer removal was done after each MTBE wash. The three organic layers were combined and further combined with 5 molar aqueous NaCl (212 kg, 9.42 kg/kg compound 8A) and stirred for at least 10 minutes. The admixture was allowed to settle for at least 10 minutes and the bottom aqueous layer was removed. The organic layer was combined with 5 molar aqueous NaCl (212 kg, 9.42 kg/kg compound 8A) and stirred for at least 10 minutes. The admixture was allowed to settle for at least 10 minutes and the bottom aqueous layer was removed. The organic layer remaining in the reactor was distilled under atmospheric pressure to reduce the volume to a minimum stir volume (about lL/kg compound 8A). The reactor contents were then further distilled under reduced pressure (50-100 mbar) and compound 8B was collected as an 80-90 °C fraction. The yield of compound 8A was 76.6% and the HPLC purity by method MTH-003 was 95.71% by HPLC Method 003 V01.

References:

WO2019/164778,2019,A1 Location in patent:Paragraph 0450; 0452-0454

81290-20-2 Synthesis