ChemicalBook CAS DataBase List 4-Chloro-6-ethyl-5-fluoropyrimidine

4-Chloro-6-ethyl-5-fluoropyrimidine synthesis

7synthesis methods

Product Name:4-Chloro-6-ethyl-5-fluoropyrimidine
CAS Number:137234-74-3
Molecular formula:C6H6ClFN2
Molecular Weight:160.58

137234-87-8

137234-74-3

Example 1: Synthesis of 4-chloro-6-ethyl-5-fluoropyrimidine <1-1> Preparation of 4-chloro-6-ethyl-5-fluoropyrimidine 80 g of 6-ethyl-5-fluoropyrimidin-4(3H)-one was dissolved in a solvent mixture of 240 mL of dichloromethane and 57.4 mL of N,N-dimethylformamide. Subsequently, 78.24 mL of triethylamine was added to the solution as a base. Phosphoryl chloride (POCl3) was slowly added dropwise to the reaction system over a period of 30 minutes. The reaction mixture was stirred under reflux conditions for 5 hours to ensure complete reaction, after which it was cooled to room temperature. 352 mL of 3N hydrochloric acid solution was carefully added to the reaction mixture at a controlled temperature not exceeding 20°C. The aqueous phase was extracted with 100 mL of dichloromethane and the organic layers were combined and washed with 100 mL of water. The organic layer was dried over anhydrous magnesium sulfate and concentrated under reduced pressure to afford the oily target product 4-chloro-6-ethyl-5-fluoropyrimidine (85.9 g, 95% yield). 1H-NMR (300 MHz, CDCl3) δ (ppm): 8.70 (1H, s), 2.90 (2H, q), 1.34 (3H, t).

137234-87-8
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137234-74-3
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Yield:137234-74-3 99%

Reaction Conditions:

with triethylamine;trichlorophosphate in dichloromethane at 48; for 6 h;Product distribution / selectivity;Industry scale;Heating / reflux;

Steps:

2
A reactor was charged with dichloromethane (20 I) and 6-ethyl-5- fluoropyrimidin-4(1 H)-one (5.00 kg, 35.2 mol) at 25-30 ⁰C. The reaction mixture was stirred for 15 min, and triethylamine (3.60 kg, 35.6 mol) was added. Phosphorus oxychloride (5.95 kg, 38.8 mol) was added over 3 h, while the reaction temperature was kept below 35 ⁰C. The reaction mass was heated at reflux (40-48 ⁰C) for 3 h. The mixture was cooled to 5 ⁰C, and hydrochloric acid (3.7 M, 20 I, 74 mol) was added over 1 h. The mixture was stirred for 30 min at 20 ⁰C. The layers were separated, and the aqueous layer was extracted twice with dichloromethane (2 x 5.0 I). The combined organic layers were washed with water (5.0 I), and the solvents were removed at reduced pressure (550 mmHg) at 28-46 ⁰C. 5.61 kg (99% yield) of the title compound was obtained as a brown liquid. Purity, HPLC: 99.6%.

References:

AXELLIA PHARMACEUTICALS APS WO2009/24214, 2009, A1 Location in patent:Page/Page column 3-4

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137234-87-8
240 suppliers
$9.00/1g

137234-74-3
336 suppliers
$10.00/1g

References

188416-35-5 Synthesis