Ethyl 2-chloropyrimidine-5-carboxylate synthesis

9synthesis methods

Product Name:Ethyl 2-chloropyrimidine-5-carboxylate
CAS Number:89793-12-4
Molecular formula:C7H7ClN2O2
Molecular Weight:186.6

A mixture of 1,2-Dihydro-2-oxo-5-pyrimidinecarboxylic acid ethyl ester (3.60 g, 21 mmol), phosphorus oxychloride (25 mL), and N, N-dimethylaniline (2.5 mL) was heated to reflux for 1.5 h. After removal of the solvent, ice water (10 mL) was added to the residue. The mixture was added to 2 N NaOH (90 ml) and extracted with EtOAc. After work, the residue was purified by column chromatography on silica gel (ethyl acetate in petroleum ether, 5 per cent v/v) to give the product Ethyl 2-chloropyrimidine-5-carboxylate (1.20 g, 30 per cent).

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89793-12-4
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Yield:89793-12-4 52%

Reaction Conditions:

with N,N-dimethyl-aniline;trichlorophosphate for 2 h;Reflux;

Steps:

1.d Step d: Ethyl 2-chloropyrimidine-5-carboxylate (Compound R-2-1)
Step d:
Ethyl 2-chloropyrimidine-5-carboxylate (Compound R-2-1)
A mixture of compound 204 (38.0 g, 153 mmol) and phosphoryl trichloride (300 mL) and N,N-dimethylaniline (3 mL) was heated at reflux for 2 h, cooled to room temperature and concentrated.
The residue was quenched carefully with ice-water, adjusted pH to 7-8 with sodium carbonate and extracted with EtOAc.
The combined organics were washed with ice-water and brine, dried over Na₂SO₄, evaporated, and purified by column chromatography (eluted with EtOAc/Hexanes, 10%) to afford compound R-2-1 (15 g, 52%) as a white solid. LCMS: 187 [M+1]⁺. ¹H NMR (400 MHz, CDCl₃): δ 1.36 (t, J=7.5 Hz, 3H), 4.39 (q, J=7.5 Hz, 2H), 9.08 (s, 2H).

References:

Curis, Inc.;Cai, Xiong;Zhai, Haixiao;Lai, Chengjung;Qian, Changgeng;Bao, Rudi US9249156, 2016, B2 Location in patent:Page/Page column 34

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95928-49-7
93 suppliers
$45.00/50mg

89793-12-4
237 suppliers
$6.00/100mg

References

763-69-9 Synthesis