Sodium borohydride → 1-Piperidinecarboxylicacid,4-hydroxy-2-methyl-,1,1-dimethylethylester,(2S,4S)-(9CI)

HRID 1051747ノート

反応式

HRID 1051747 の反応式
[BH4-].[Na+].[CH3:3][CH:4]1[CH2:9][C:8](=[O:10])[CH2:7][CH2:6][N:5]1[C:11]([O:13][C:14]([CH3:17])([CH3:16])[CH3:15])=[O:12]>C(O)C>[OH:10][C@H:8]1[CH2:7][CH2:6][N:5]([C:11]([O:13][C:14]([CH3:17])([CH3:16])[CH3:15])=[O:12])[C@@H:4]([CH3:3])[CH2:9]1.[OH:10][C@@H:8]1[CH2:7][CH2:6][N:5]([C:11]([O:13][C:14]([CH3:17])([CH3:16])[CH3:15])=[O:12])[C@@H:4]([CH3:3])[CH2:9]1

参加物

5

反応物 2

HCID 4311764Sodium borohydrideHCID 12992764tert-Butyl 2-methyl-4-oxopiperidine-1-carboxylate

生成物 2

HCID 450974401-Piperidinecarboxylicacid,4-hydroxy-2-methyl-,1,1-dimethylethylester,(2S,4S)-(9CI)収率 36%HCID 450974411-Piperidinecarboxylicacid,4-hydroxy-2-methyl-,1,1-dimethylethylester,(2S,4R)-(9CI)収率 20%

試薬・触媒・溶媒 1

HCID 702Ethanol溶媒

実験手順

Following the procedure found in Plettenburg, Oliver et. Al (PCT Int. Appl., 2007012421), sodium borohydride (213 mg, 5.6 mmol) was added portion-wise to a solution of tert-butyl 2-methyl-4-oxopiperidine-1-carboxylate (1.0 g, 4.7 mmol) in ethanol (10 mL). The mixture was stirred at room temperature for 2 h. The solution was concentrated in vacuo and then partitioned between water (40 mL) and ethyl acetate (40 mL). The aqueous layer was extracted twice with ethyl acetate (40 mL). The combined organic layers were washed with brine (20 mL), dried over anhydrous sodium sulfate, filtered, and concentrated in vacuo. The residue was purified via column chromatography on silica gel (Biotage 50 g column, gradient elution with 40-50% ethyl acetate in hexanes) to afford (rac)-tert-butyl (cis)-4-hydroxy-2-methylpiperidine-1-carboxylate (367 mg, 36%) and (rac)-tert-butyl (trans)-4-hydroxy-2-methylpiperidine-1-carboxylate (205 mg, 20%) as white solids.

後処理

  1. concentrationThe solution was concentrated in vacuo
  2. custompartitioned between water (40 mL) and ethyl acetate (40 mL)
  3. extractionThe aqueous layer was extracted twice with ethyl acetate (40 mL)
  4. washThe combined organic layers were washed with brine (20 mL)
  5. dry with materialdried over anhydrous sodium sulfate
  6. filtrationfiltered
  7. concentrationconcentrated in vacuo
  8. customThe residue was purified via column chromatography on silica gel (Biotage 50 g column, gradient elution with 40-50% ethyl acetate in hexanes)

出典と根拠

ORDレコード
ord-bd77bf5511e34bcd9e43fc4f71453bb7
出典データセット
uspto-grants-2016_07
特許番号
US09388161B2

反応ノート

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