Toluene → tert-Butyl (1S,3S,5S)-3-(hydroxymethyl)-2-azabicyclo[3.1.0]hexane-2-carboxylate

HRID 2064789Notes

Reaction equation

HRID 2064789 reaction equation
CC(C[AlH]CC(C)C)C.C1(C)C=CC=CC=1.C([O:19][C:20]([C@@H:22]1[CH2:27][C@H:26]2[C@H:24]([CH2:25]2)[N:23]1[C:28]([O:30][C:31]([CH3:34])([CH3:33])[CH3:32])=[O:29])=O)C.[OH-].[Na+]>C1COCC1.CCOC(C)=O>[C:31]([O:30][C:28]([N:23]1[C@H:22]([CH2:20][OH:19])[CH2:27][C@H:26]2[C@@H:24]1[CH2:25]2)=[O:29])([CH3:34])([CH3:33])[CH3:32]

Participants

7

Reactant 4

HCID 1140TolueneHCID 14487Diisobutylaluminum hydrideHCID 14798Sodium HydroxideHCID 50987983(1S,3S,5S)-2-Tert-butyl 3-ethyl 2-azabicyclo[3.1.0]hexane-2,3-dicarboxylate

Product 1

HCID 10899963tert-Butyl (1S,3S,5S)-3-(hydroxymethyl)-2-azabicyclo[3.1.0]hexane-2-carboxylate

Reagents, catalysts & solvents 2

HCID 8028TetrahydrofuranSolventHCID 8857Ethyl AcetateSolvent

Procedure

At −78° C. a solution of DIBAL in toluene (1.0 M, 47 mmol, 47 mL) is added dropwise to a solution of (1S,3S,5S)-2-aza-bicyclo[3.1.0]hexane-2,3-dicarboxylic acid 2-tert-butyl ester 3-ethyl ester (21.4 mmol) in THF (60 mL). After 50 min the mixture is allowed to reach RT, stirred for additional 50 min and poured into a mixture of aqueous NaOH solution (1.0 M) and ice. EtOAc is added, the layers are separated and the aqueous layer is extracted with EtOAc (3×70 mL). The combined organic layers are washed with aqueous NaOH solution (1.0 M) and brine, dried over Na2SO4 and concentrated in vacuo to give the desired alcohol as a colourless oil. LC-MS (acidic): tR=0.79 min; [M+H]+=214.3.

Workup

  1. customto reach RT
  2. customthe layers are separated
  3. extractionthe aqueous layer is extracted with EtOAc (3×70 mL)
  4. washThe combined organic layers are washed with aqueous NaOH solution (1.0 M) and brine
  5. dry with materialdried over Na2SO4
  6. concentrationconcentrated in vacuo

Sources & evidence

ORD record
ord-8b414de383114a67bb80861c33f34d50
Source dataset
uspto-grants-2012_10
Patent number
US08288435B2

Reaction notes

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