Reaction #1121787

Reaction equation

4-fluorobenzoic acid

diisopropylethylamine

HOBT

HBTU

N,O-dimethyl hydroxylamine hydrochloride

→

4-fluoro-N-methoxy-N-methyl-benzamide

Yield 79.0%

4-Fluoro-N-methoxy-N-methyl-benzamide

Yield 79.0%

Solvents

DMF

EtOAc

Conditions

Workup

1. 1
   workup.STIRRINGAfter stirring at room temperature for 2 hours
2. 2
   Washwashed with 4×50 mL of water
3. 3
   ConcentrationThe combined organic layers is concentrated
4. 4
   Otherpurified by flash column chromatography (hexane 70%, EtOAc 30%)

Procedure

To a solution of 4-fluorobenzoic acid (6.8 g, 48.57 mmole) in 100 mL of DMF at room temperature, is added diisopropylethylamine (25.3 mL, 145.7 mmole). After stirring at room temperature for 20 minutes, HOBT (7.22 g, 53.43 mmole), HBTU (20.26 g, 53.43 mmole) and N,O-dimethyl hydroxylamine hydrochloride (5.69 g, 58.29 mmole) are added to the reaction solution. After stirring at room temperature for 2 hours, the reaction solution is diluted with 200 mL of EtOAc and washed with 4×50 mL of water. The combined organic layers is concentrated and purified by flash column chromatography (hexane 70%, EtOAc 30%) to yield 4-fluoro-N-methoxy-N-methyl-benzamide (4a) (7.0 g, yield 79%).

Source