Toluene → tert-butyl (1R,3S,4S)-3-(hydroxymethyl)-2-azabicyclo[2.2.1]heptane-2-carboxylate

HRID 882792ノート

反応式

HRID 882792 の反応式
CC(C[AlH]CC(C)C)C.C1(C)C=CC=CC=1.C[O:18][C:19]([C@@H:21]1[C@@H:26]2[CH2:27][C@@H:23]([CH2:24][CH2:25]2)[N:22]1[C:28]([O:30][C:31]([CH3:34])([CH3:33])[CH3:32])=[O:29])=O.[OH-].[Na+]>C1COCC1.CCOC(C)=O>[C:31]([O:30][C:28]([N:22]1[C@H:21]([CH2:19][OH:18])[C@@H:26]2[CH2:27][C@H:23]1[CH2:24][CH2:25]2)=[O:29])([CH3:34])([CH3:32])[CH3:33]

参加物

7

反応物 4

HCID 1140TolueneHCID 14487Diisobutylaluminum hydrideHCID 14798Sodium HydroxideHCID 66866671(1R, 3S, 4S)-2-Boc-2-aza-bicyclo[2.2.1]heptane-3-carboxylic acid methyl ester

生成物 1

HCID 66866104tert-butyl (1R,3S,4S)-3-(hydroxymethyl)-2-azabicyclo[2.2.1]heptane-2-carboxylate

試薬・触媒・溶媒 2

HCID 8028Tetrahydrofuran溶媒HCID 8857Ethyl Acetate溶媒

実験手順

At −78° C. a solution of DIBAL in toluene (1.7M, 137 mmol) is added dropwise to a solution of (1R,3S,4S)-2-aza-bicyclo[2.2.1]heptane-2,3-dicarboxylic acid 2-tert-butyl ester 3-methyl ester (61.0 mmol) in THF (180 mL). After 80 min the solution is allowed to reach rt, stirred for additional 2 h and poured into a mixture of aq. NaOH solution (1.0M, 200 mL) and ice. EtOAc (150 mL) is added, the layers are separated and the aq. layer is extracted three times with EtOAc (150 mL each). The combined organic layers are washed with aq. NaOH solution (1.0M) and brine, dried over Na2SO4 and concentrated in vacuo to give a crude product which is used without further purification. LC-MS (basic): tR=0.78 min; [M+H]+=228.3.

後処理

  1. customto reach rt
  2. customthe layers are separated
  3. extractionthe aq. layer is extracted three times with EtOAc (150 mL each)
  4. washThe combined organic layers are washed with aq. NaOH solution (1.0M) and brine
  5. dry with materialdried over Na2SO4
  6. concentrationconcentrated in vacuo

出典と根拠

ORDレコード
ord-b2ce05038b2d4ac8b03cfccf3bfcfb4d
出典データセット
uspto-grants-2012_08
特許番号
US08236801B2

反応ノート

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