4-Chloro-5-fluoro-2-nitrobenzoic Acid Methyl Ester synthesis

Yield:-

Reaction Conditions:

Stage #1:4-chloro-3-fluorobenzoic acid with sulfuric acid;sodium nitrite at 0 - 20;
Stage #2:methanol at 0 - 100; for 4.5 h;

Steps:

13A.1
EXAMPLE 13APreparation of compound 2010Step 1 :To a mixture of 4-chloro-3-fluorobenzoic acid 13a1 (2.0O g, 1 1.5 mmol) in concentrated H₂SO₄ (15 mL) chilled to O⁰C is added NaNO₂ (1.16 g, 1 1 5 mmol) portion-wise. Once the addition of NaNO₂ is complete, the mixture is allowed to warm to RT and stirred overnight. The mixture is chilled to O⁰C once again and MeOH (20 mL) is added carefully. The ice bath is removed and the mixture is heated to 100⁰C and stirred for about 4.5 hours. The mixture is carefully diluted into a water/ice mixture. The aqueous mixture is made basic by the addition of NaHCO₃ then is partitioned with EtOAc The organic layer is separated then washed with water and brine, dried over MgSO₄, filtered and concentrated under reduced pressure. Crude nitro-ester 13a2 is utilized without further purification.

References:

BOEHRINGER INGELHEIM INTERNATIONAL GMBH WO2009/18657, 2009, A1 Location in patent:Page/Page column 66