Reacción #48801

Ecuación de reacción

lithium hydroxide monohydrate

methyl 3-hydroxy-5-[(1S)-2-hydroxy-1-methylethoxy]benzoate

cesium carbonate

1-(3,4-difluorobenzoyl)azetidine

→

desired compound

3-[4-(Azetidin-1-ylcarbonyl)-2-fluorophenoxy]-5-[(1S)-2-hydroxy-1-methylethoxy]benzoic acid

Disolventes

water

Water

diethyl ether ethyl acetate

water

dimethylacetamide

Condiciones de reacción

Tratamiento posterior

1. 1
   TemperaturaThe reaction mixture was cooled
2. 2
   Extracciónthe mixture extracted with ethyl acetate (3×50 mL)
3. 3
   Otroto remove any ester
4. 4
   Extracciónextracted into ethyl acetate (5×50 mL)
5. 5
   Lavadowashed with water (100 mL), brine (100 mL)
6. 6
   Secadodried (MgSO4)
7. 7
   Filtraciónfiltered
8. 8
   Otroevaporated in vacuo
9. 9
   Otroto give a yellow liquid
10. 10
    Lavadothe solution washed with water (100 mL), brine (100 mL)
11. 11
    Secadodried (MgSO4)
12. 12
    Filtraciónfiltered
13. 13
    Otroevaporated in vacuo

Procedimiento

A suspension of methyl 3-hydroxy-5-[(1S)-2-hydroxy-1-methylethoxy]benzoate (10.65 g, 0.047 mmol), cesium carbonate (30.71 g, 0.094 mol) and 1-(3,4-difluorobenzoyl)azetidine (9.28 g, 0.047 mol) in dimethylacetamide (80 mL) was heated at 120° C. for 22 hours. The reaction mixture was cooled and water (60 mL) added followed by lithium hydroxide monohydrate (1.97 g, 0.047 mol) in water (45 mL). The reaction was stirred for a further 24 hours. Water (100 mL) was added and the mixture extracted with ethyl acetate (3×50 mL) to remove any ester. The aqueous layer was acidified and extracted into ethyl acetate (5×50 mL). The extracts were combined and washed with water (100 mL), brine (100 mL), dried (MgSO4), filtered, and evaporated in vacuo to give a yellow liquid. A diethyl ether/ethyl acetate mixture (3:1) was added and the solution washed with water (100 mL), brine (100 mL), dried (MgSO4), filtered and evaporated in vacuo to give the desired compound. (9.8 g)

Fuente