ChemicalBook CAS DataBase List Methyl 4-methoxyacetoacetate

Methyl 4-methoxyacetoacetate synthesis

9synthesis methods

Product Name:Methyl 4-methoxyacetoacetate
CAS Number:41051-15-4
Molecular formula:C6H10O4
Molecular Weight:146.14

Methyl 4-methoxyacetoacetate is used as a pharmaceutical and pesticide intermediate, mainly in the synthesis of dolutegravir sodium. It can be synthesized by the condensation reaction of Methyl 4-chloro-3-oxo-butanoate and Methanol.

67-56-1 Synthesis

67-56-1
751 suppliers
$7.29/5ml-f

32807-28-6
263 suppliers
$10.00/5g

41051-15-4
302 suppliers
$6.00/5g

Yield:41051-15-4 93%

Reaction Conditions:

Stage #1:methanol with sodium hydride in tetrahydrofuran at 20;
Stage #2:Methyl 4-chloroacetoacetate in tetrahydrofuran at 20;

Steps:

General procedure h (adapted from S. Mitsuhashi et al, J. Am. Chem. Soc. 2008, 130, 4140).
General procedure: To a suspension of sodium hydride (2.2 eq) in THF (0.5 M) at RT, an alcohol (1.1 eq) was added dropwise. The mixture was stirred for 5 min before methyl 4-chloro-3-oxobutanoate (1 eq) was dropwise added. This mixture was stirred for 30 min and then concentrated in vacuum. Water was added, and the pH was adjusted to 6-7 by the addition of 2N aq. HCl. The resulting mixture was extracted with dichloromethane (×2) and ethyl acetate (×2), and the combined organic layers were washed with brine, dried (Na₂SO₄), filtered and concentrated. The resulting residue was purified by flash column chromatography on silica gel using ethyl acetate/hexane as eluent to afford the corresponding dicarbonyl compound.

References:

Oncostellae, S.L.;KURZ, Guido;CAMACHO GóMEZ, Juan EP3480201, 2019, A1 Location in patent:Paragraph 0288; 0289; 0291; 0292

FullText

32807-28-6
263 suppliers
$10.00/5g

41051-15-4
302 suppliers
$6.00/5g

References