5-Pyrimidineacetic acid, 4,6-dichloro-, methyl ester

5-Pyrimidineacetic acid, 4,6-dichloro-, methyl ester - Names and Identifiers

Name	Methyl 2-(4,6-dichloropyrimidin-5-yl)acetate
Synonyms	Methyl 4,6-Dichloropyrimidine-5-acetate Methyl 2-(4,6-dichloropyriMidin-5-yl)acetate methyl-2-(4,6-dichloropyriMidin-5-yl)acetate Methyl 2-(4,6-dichloropyrimidin-5-yl)acetate 5-Pyrimidineacetic acid, 4,6-dichloro-, methyl ester
CAS	171096-33-6

5-Pyrimidineacetic acid, 4,6-dichloro-, methyl ester - Physico-chemical Properties

Molecular Formula	C7H6Cl2N2O2
Molar Mass	221.04
Density	1.448±0.06 g/cm3(Predicted)
Boling Point	305.9±37.0 °C(Predicted)
pKa	-4.41±0.50(Predicted)
Storage Condition	under inert gas (nitrogen or Argon) at 2-8°C

5-Pyrimidineacetic acid, 4,6-dichloro-, methyl ester - Reference Information

application

4, 6-dichloropyrimidin-5-methyl acetate is a pharmaceutical intermediate, which can be prepared from diethyl malonate and ethyl bromoacetate as starting materials in three steps, and can be used in laboratory research and development processes and chemical production processes.

Preparation

Step 1. ethane -1,1, 2-tricarboxylic triethyl ester: 400 liters of acetone is loaded into the reactor. Fill 71.17kg of powdered potassium carbonate to keep the temperature at 25-30 ℃. 55kg of diethyl malonate was loaded into the reactor under stirring to keep the temperature at 25-30°C. The reaction was heated at 55-60°C for 2.5 hours. The reaction was cooled to 50-54°C and 5.225kg of sodium iodide was slowly added to the reactor, keeping the temperature at 52-54°C. 71.5kg ethyl bromoacetate was added slowly to keep the temperature at 52-54 ℃. Stir for 12-14 hours to keep the temperature at 55-60°C (reflux). The reaction was cooled to 10-15°C, the reaction material was filtered and the resulting filter cake was washed with 110 liters of acetone (at 10-15°C). The filtrate is loaded into the reactor, heated to 45-50°C and concentrated until no distillate is visible. A vacuum was applied to the concentrated distillate and an excess of unreacted diethyl malonate was distilled at an external temperature of 80°C under a vacuum (0.4-0.5 mmHg). The temperature was increased to 135°C and the product was distilled to provide 45.5kg of triethyl ethane -1,1, 2-tricarboxylate (53.72%) with a purity of 93.2% by GC. Step 2. 2-(4, 6-dihydroxypyrimidine-5-yl) methyl acetate to add ethane -1,1, 2-tricarboxylic triethyl ester (74.75g; 1.00 equivalent; 303.54 mmol; 69.41 ml) to sodium methoxide (139.6 ml 25% wt, 4.35M in MeOH)(131.2g; 2.00 equivalent; 607 mmol) in a solution of methanol (224.8 ml), followed by addition of formamidine hydrochloride (25.19g, 1.01 equivalent; 306.58 mmol) at room temperature. Stir this mixture overnight. Acidification with 37% HCl at 0°C; filter the solids and dry overnight in a vacuum to produce a white solid-like title compound (55.89g; 99.99% yield). 1H NMR (300 MHz, DMSO): 8.03 (s, 1H), 3.55 (s, 3H), 3.24-3.15 (m, 2H). Step A suspension of 2-(4,6-dihydroxypyrimidin-5-yl) methyl acetate (46.65g; 1.00 equivalents; 253.33 millimoles) was added to phosphoryl chloride (235.41 ml; 10.00 equivalents; 2.53 moles) 3. to methyl 4, 6-dichloropyrimidin-5-acetate and stirred under reflux for 3 hours. Distill to 1/3 of the original volume under vacuum and pour the mixture into 4°C aqueous solution of dipotassium hydrogen phosphate (2M)(2.53 liters; 20 equivalents; 5.07 moles). Extraction with EA, drying with MgSO4, filtration and concentration in vacuum. The crude product was purified by silica plug using DCM as eluent to produce a light yellow solid title compound (30.32g; 137.17 mmol; 54.15% yield).

Last Update：2024-04-09 02:00:07