2-Fluoropyridine → benzyl 4-(2-fluoropyridin-3-yl)-4-hydroxypiperidine-1-carboxylate

HRID 2256066노트

반응식

HRID 2256066 반응식
C([N-]C(C)C)(C)C.[Li+].[F:9][C:10]1[CH:15]=[CH:14][CH:13]=[CH:12][N:11]=1.[Br-].[Li+].[CH2:18]([O:25][C:26]([N:28]1[CH2:33][CH2:32][C:31](=[O:34])[CH2:30][CH2:29]1)=[O:27])[C:19]1[CH:24]=[CH:23][CH:22]=[CH:21][CH:20]=1>O1CCCC1.O.CCCCCC>[CH2:18]([O:25][C:26]([N:28]1[CH2:33][CH2:32][C:31]([OH:34])([C:15]2[C:10]([F:9])=[N:11][CH:12]=[CH:13][CH:14]=2)[CH2:30][CH2:29]1)=[O:27])[C:19]1[CH:24]=[CH:23][CH:22]=[CH:21][CH:20]=1

참가 물질

8

반응물 4

HCID 97462-FluoropyridineHCID 82050Lithium BromideHCID 643496Benzyl 4-oxopiperidine-1-carboxylateHCID 2724682Lithium diisopropylamide

생성물 1

HCID 12016071benzyl 4-(2-fluoropyridin-3-yl)-4-hydroxypiperidine-1-carboxylate

시약·촉매·용매 3

HCID 962Water용매HCID 8028Tetrahydrofuran용매3회HCID 8058Hexane용매

반응 조건

온도
-50 °C

실험 절차

To a solution of lithium diisopropylamide (0.31 mol) in 300 mL of anhydrous tetrahydrofuran:hexane at -78° C. was added a solution of 2-fluoropyridine (24.6 mL) in 40 mL of anhydrous tetrahydrofuran. The reaction mixture was allowed to warm to -50° C., cooled back to -74° C. and treated dropwise with a solution of lithium bromide (55.5 g) and 1-benzyloxycarbonyl-4-oxopiperidine (55.5 g) in 300 mL of anhydrous tetrahydrofuran so that the temperature of the reaction mixture remained below -70° C. After the addition was complete, the reaction mixture was allowed to warm to -30° C. and then treated with water. The organic layer was separated and the aqueous layer was extracted with two portions of ether. Combined organic layers were dried and evaporated to afford the crude product. This material was purified by column chromatography to afford the pure product.

후처리

  1. temperaturecooled back to -74° C.
  2. customremained below -70° C
  3. additionAfter the addition
  4. temperatureto warm to -30° C.
  5. customThe organic layer was separated
  6. extractionthe aqueous layer was extracted with two portions of ether
  7. customCombined organic layers were dried
  8. customevaporated

출처 및 근거

ORD 기록
ord-18d71a69368e48e4b1b44523334e0e52
출처 데이터셋
uspto-grants-1997_08
특허 번호
US05654299

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