反応 #48173

反応方程式

sodium acetoxyborohydride

(4,4-difluoro-piperidin-1-yl)-[5-(piperidin-4-yloxy)-1H-indol-2-yl]-methanone

(4,4-Difluoro-piperidin-1-yl)-[5-(piperidin-4-yloxy)-1H-indol-2-yl]-methanone

acetic acid

cyclobutanone

→

desired product

[5-(1-Cyclobutyl-piperidin-4-yloxy)-1H-indol-2-yl]-(4,4-difluoro-piperidin-1-yl)-methanone

溶媒

water

ethyl acetate

tetrahydrofuran

反応条件

後処理

1. 1
   workup.STIRRINGthe mixture stirred for 16 h at 65° C
2. 2
   抽出The aqueous layer was extracted twice with ethyl acetate
3. 3
   洗浄the combined organic fractions were washed twice with saturated sodium bicarbonate solution
4. 4
   乾燥dried over sodium sulfate
5. 5
   ろ過filtered
6. 6
   その他evaporated to dryness
7. 7
   その他purified on silica gel
8. 8
   洗浄eluting with a 49:1:0 to 95:5:0.25 gradient of dichloromethane/methanol/ammonium hydroxide

実験手順

A mixture of (4,4-difluoro-piperidin-1-yl)-[5-(piperidin-4-yloxy)-1H-indol-2-yl]-methanone (example 43, step 6, 350 mg, 1.0 eq.), acetic acid (0.17 mL, 3.0 eq.) and cyclobutanone (138 mg, 2.0 eq.) in tetrahydrofuran (6 mL) was stirred at 55° C. for 1 h. At room temperature, sodium acetoxyborohydride (421 mg, 2.0 eq.) was added and the mixture stirred for 16 h at 65° C. The reaction mixture was partitionned between ethyl acetate and water. The aqueous layer was extracted twice with ethyl acetate and the combined organic fractions were washed twice with saturated sodium bicarbonate solution, dried over sodium sulfate, filtered, evaporated to dryness and purified on silica gel, eluting with a 49:1:0 to 95:5:0.25 gradient of dichloromethane/methanol/ammonium hydroxide, to yield 265 mg (65%) from the desired product as off-white solid. MS (m/e): 418.1 (MH+, 100%).

出典