تفاعل #48123

معادلة التفاعل

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

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

intermediate 1

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

lithium bis-(trimethylsilyl)amide

methylchloroformate

→

desired product

المردود 15.7%

2-(4,4-Difluoro-piperidine-1-carbonyl)-5-(1-isopropyl-piperidin-4-yloxy)-indole-1-carboxylic acid methyl ester

المردود 15.7%

المذيبات

brine

tetrahydrofuran

ظروف التفاعل

المعالجة

1. 1
   استخلاصextracted with dichloromethane
2. 2
   تجفيفdried over sodium sulfate
3. 3
   ترشيحfiltered
4. 4
   أخرىevaporated to dryness
5. 5
   أخرىpurified on silica gel
6. 6
   غسيلeluting with a 98:2 to 97:3 gradient of dichloromethane/methanol

الإجراء التجريبي

A solution of (4,4-difluoro-piperidin-1-yl)-[5-(1-isopropyl-piperidin-4-yloxy)-1H-indol-2-yl]-methanone (intermediate 1, 100 mg, 1.0 eq.), lithium bis-(trimethylsilyl)amide (1M solution in tetrahydrofuran, 271 ul, 1.1 eq.) and methylchloroformate (26 mg, 1.1 eq.) in tetrahydrofuran (2 mL) was stirred at room temperature for 48 h, then poured into brine, extracted with dichloromethane, dried over sodium sulfate, filtered, evaporated to dryness and purified on silica gel, eluting with a 98:2 to 97:3 gradient of dichloromethane/methanol, to yield 18 mg (15%) of the desired product as yellow oil. MS (m/e): 464.2 (MH+, 100%).

المصدر