Sodium hydride → tert-Butyl (3R)-3-(2-tert-butoxy-2-oxoethoxy)pyrrolidine-1-carboxylate

HRID 51305ノート

反応式

HRID 51305 の反応式
[H-].[Na+].[OH:3][C@@H:4]1[CH2:8][CH2:7][N:6]([C:9]([O:11][C:12]([CH3:15])([CH3:14])[CH3:13])=[O:10])[CH2:5]1.Br[CH2:17][C:18]([O:20][C:21]([CH3:24])([CH3:23])[CH3:22])=[O:19]>O1CCCC1>[C:21]([O:20][C:18](=[O:19])[CH2:17][O:3][C@@H:4]1[CH2:8][CH2:7][N:6]([C:9]([O:11][C:12]([CH3:15])([CH3:14])[CH3:13])=[O:10])[CH2:5]1)([CH3:24])([CH3:23])[CH3:22]

参加物

5

反応物 3

HCID 24758Sodium hydrideHCID 79177tert-Butyl bromoacetateHCID 6544479tert-Butyl (3R)-3-hydroxypyrrolidine-1-carboxylate

生成物 1

HCID 22883149tert-Butyl (3R)-3-(2-tert-butoxy-2-oxoethoxy)pyrrolidine-1-carboxylate

試薬・触媒・溶媒 1

HCID 8028Tetrahydrofuran溶媒

実験手順

Sodium hydride (704 mg, 60% in mineral oil, 17.6 mmol) was added to an ice-cooled solution of tert-butyl (3R)-3-hydroxypyrrolidine-1-carboxylate (J. Med. Chem. 1998, 41(25), 4983) (5 g, 26.7 mmol) in tetrahydrofuran (100 ml), and the mixture was allowed to warm to room temperature and stirred for 20 minutes. tert-Butyl bromoacetate (5.2 g, 26.7 mmol) was added and the mixture was heated under reflux for 18 hours, then cooled and concentrated under reduced pressure. The residue was partitioned between ethyl acetate and water and the phases separated. The organic layer was dried (MgSO4) and evaporated under reduced pressure. The crude product was purified by column chromatography on silica gel using an elution gradient of ethyl acetate:pentane (0:100 to 20:80) to afford the title compound, 1.95 g.

後処理

  1. temperaturethe mixture was heated
  2. temperatureunder reflux for 18 hours
  3. temperaturecooled
  4. concentrationconcentrated under reduced pressure
  5. customThe residue was partitioned between ethyl acetate and water
  6. customthe phases separated
  7. dry with materialThe organic layer was dried (MgSO4)
  8. customevaporated under reduced pressure
  9. customThe crude product was purified by column chromatography on silica gel using an elution gradient of ethyl acetate:pentane (0:100 to 20:80)

出典と根拠

ORDレコード
ord-23868278190249838fbe898e76c2ccc0
出典データセット
uspto-grants-2004_03
特許番号
US06713496B2

反応ノート

読み込み中…