Diethyl Ether → (S)-tert-Butyl 3-((S)-1-hydroxy-3-methylbutyl)pyrrolidine-1-carboxylate

HRID 1671379ノート

反応式

HRID 1671379 の反応式
[C:1]([O:5][C:6]([N:8]1[CH2:12][CH2:11][C@H:10]([CH:13]=[O:14])[CH2:9]1)=[O:7])([CH3:4])([CH3:3])[CH3:2].C1COCC1.[CH2:20]([Mg]Cl)[CH:21]([CH3:23])[CH3:22].CCOCC>[NH4+].[Cl-]>[C:1]([O:5][C:6]([N:8]1[CH2:12][CH2:11][C@H:10]([C@@H:13]([OH:14])[CH2:20][CH:21]([CH3:23])[CH3:22])[CH2:9]1)=[O:7])([CH3:4])([CH3:3])[CH3:2].[C:1]([O:5][C:6]([N:8]1[CH2:12][CH2:11][C@H:10]([C@H:13]([OH:14])[CH2:20][CH:21]([CH3:23])[CH3:22])[CH2:9]1)=[O:7])([CH3:4])([CH3:3])[CH3:2]

参加物

7

反応物 4

HCID 3283Diethyl EtherHCID 8028TetrahydrofuranHCID 1514343(S)-tert-butyl 3-formylpyrrolidine-1-carboxylateHCID 178418368HCID 178418368、化合物

生成物 2

HCID 57347268(S)-tert-Butyl 3-((S)-1-hydroxy-3-methylbutyl)pyrrolidine-1-carboxylateHCID 66745537(S)-3-((R)-1-hydroxy-3-methylbutyl)pyrrolidine-1-carboxylic acid t-butyl ester

試薬・触媒・溶媒 1

HCID 25517Ammonium Chloride溶媒

反応条件

温度
-78 °C

実験手順

(S)-3-Formylpyrrolidine-1-carboxylic acid t-butyl ester (6.0 g, 30.1 mmol) and THF (60 mL, 700 mmol) were combined under nitrogen, and the resulting solution was cooled to −78° C. 2.0M Isobutylmagnesium chloride in ether (18.1 mL, 36.1 mmol) was then added dropwise over 10 minutes. The mixture was allowed to warm to room temperature slowly overnight. Then aqueous saturated NH4Cl (100 mL) was added dropwise to quench the reaction. The resulting mixture was extracted with EtOAc (2×100 mL), and the combined organic layers were washed with saturated aqueous NaHCO3 (1×100 mL) and saturated aqueous NaCl (1×100 mL), then dried over anhydrous MgSO4, filtered, and concentrated in vacuo. The crude product was purified by column chromatography (80 g SiO2, ethyl ether) to yield (S)-3-((S)-1-hydroxy-3-methylbutyl)pyrrolidine-1-carboxylic acid t-butyl ester (1.6 g) and (S)-3-((R)-1-hydroxy-3-methylbutyl)pyrrolidine-1-carboxylic acid t-butyl ester (2.2 g) as oils.

後処理

  1. temperatureto warm to room temperature slowly overnight
  2. customto quench
  3. customthe reaction
  4. extractionThe resulting mixture was extracted with EtOAc (2×100 mL)
  5. washthe combined organic layers were washed with saturated aqueous NaHCO3 (1×100 mL) and saturated aqueous NaCl (1×100 mL)
  6. dry with materialdried over anhydrous MgSO4
  7. filtrationfiltered
  8. concentrationconcentrated in vacuo
  9. customThe crude product was purified by column chromatography (80 g SiO2, ethyl ether)

出典と根拠

ORDレコード
ord-10546a0c81e74d1fb31977df46e44ff5
出典データセット
uspto-grants-2011_08
特許番号
US07994209B2

反応ノート

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