تفاعل #1890586

معادلة التفاعل

Ethyl-2-hydroxyisobutyrate

NaOH

NaH

1-benzyl-3-chloromethyl-1H-indazole

→

2-[1(1-benzyl-1H-indazol-3-yl)methoxy]-2-methylpropanoic acid

المذيبات

DMF

toluene

toluene

DMF

ظروف التفاعل

المعالجة

1. 1
   أخرىfitted with a mechanical stirrer and a reflux condenser under an inert atmosphere
2. 2
   أخرى(checked by TLC, approximately 10 hours)
3. 3
   درجة الحرارةAfter cooling to room temperature the mixture
4. 4
   غسيلwas washed with acidified water and water
5. 5
   تركيزThe organic phase was concentrated under reduced pressure
6. 6
   أخرىthe oily residue obtained
7. 7
   درجة الحرارةat reflux temperature for at least 3 hours
8. 8
   أخرىThe product, which was precipitated out by the addition of concentrated HCl
9. 9
   ترشيحwas filtered
10. 10
    أخرىdried

الإجراء التجريبي

Ethyl-2-hydroxyisobutyrate (18.5 g, 140 mmol, 1.2 eq.), toluene (100 mL) and DMF (20 mL) were placed in a three-necked flask fitted with a mechanical stirrer and a reflux condenser under an inert atmosphere. A dispersion of 60% NaH (5.6 g, 140 mmol, 1.2 eq.) was added to the mixture in portions over a period of approximately 1.5 hours. A solution of 1-benzyl-3-chloromethyl-1H-indazole (30 g, 117 mmol, 1 eq.) in toluene (90 mL) and DMF (60 mL) was then added dropwise. The reaction mixture was heated to approximately 90° C. and kept at that temperature until the reaction was complete (checked by TLC, approximately 10 hours). After cooling to room temperature the mixture was washed with acidified water and water. The organic phase was concentrated under reduced pressure and the oily residue obtained was treated with 10 M NaOH (36 mL) at reflux temperature for at least 3 hours. The product, which was precipitated out by the addition of concentrated HCl, was filtered and dried. Yield: 32.3 g of white solid (85%).

المصدر