Reaktion #58202

Reaktionsgleichung

N,4-dimethoxy-N-methylbenzamide

n-butyllithium

2-bromo-5-methoxybenzoic acid

cardice acetone

→

white crystals

Ausbeute 64.0%

5-methoxy-2-(4-methoxybenzoyl)benzoic acid

Ausbeute 64.0%

Lösungsmittel

THF

hexane

tetrahydrofuran

Reaktionsbedingungen

Aufarbeitung

1. 1
   Sonstigedoes not exceed −70° C
2. 2
   workup.ADDITIONAfter the addition
3. 3
   workup.STIRRINGThe reaction medium is stirred at −78° C. for 1 hour
4. 4
   Sonstigethe bath of cardice/acetone is then removed
5. 5
   workup.STIRRINGthe reaction medium is stirred
6. 6
   workup.WAITto return gradually to room temperature, for 18 hours
7. 7
   Extraktionextracted with tert-butyl methyl ether
8. 8
   workup.ADDITIONThe aqueous phase containing the carboxylate
9. 9
   Extraktionextracted with dichloromethane
10. 10
    WaschenThe dichloromethane phase is washed with brine
11. 11
    Trocknendried over anhydrous sodium sulfate
12. 12
    Filtrationfiltered
13. 13
    Sonstigeevaporated
14. 14
    SonstigeThe product is crystallized from isopropyl ether
15. 15
    Filtrationafter filtering
16. 16
    Sonstigedrying

Vorschrift

A solution of 18.5 g (80 mmol) of 2-bromo-5-methoxybenzoic acid in 150 mL of tetrahydrofuran is stirred under nitrogen at −78° C. in a bath of cardice/acetone. 100 mL (160 mmol) of a 1.6M solution of n-butyllithium in hexane are added dropwise over about 1 hour, while taking care to ensure that the temperature does not exceed −70° C. About half way through the introduction, the formation of a beige-coloured precipitate that corresponds to the formation of the lithium carboxylate is noted. After the addition, the mixture is stirred at −78° C. for 1 hour, and a solution of 15.9 g (80 mmol) of N,4-dimethoxy-N-methylbenzamide in 20 mL of THF is added dropwise. The reaction medium is stirred at −78° C. for 1 hour and the bath of cardice/acetone is then removed and the reaction medium is stirred, while allowing the temperature to return gradually to room temperature, for 18 hours. The mixture is hydrolysed with 100 mL of water, basified to pH=12 with 2N NaOH solution and then extracted with tert-butyl methyl ether. The aqueous phase containing the carboxylate is acidified with 5N HCl solution to pH 1 and extracted with dichloromethane. The dichloromethane phase is washed with brine, dried over anhydrous sodium sulfate, filtered and evaporated. The product is crystallized from isopropyl ether; after filtering and drying, 14.6 g of white crystals are obtained (yield=64%).

Quelle