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

HRID 2256066ノート

反応式

HRID 2256066 の反応式
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

参加物

8

反応物 4

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

生成物 1

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

試薬・触媒・溶媒 3

HCID 962Water溶媒HCID 8028Tetrahydrofuran溶媒3 回HCID 8058Hexane溶媒

反応条件

温度
-50 °C

実験手順

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.

後処理

  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

出典と根拠

ORDレコード
ord-18d71a69368e48e4b1b44523334e0e52
出典データセット
uspto-grants-1997_08
特許番号
US05654299

反応ノート

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