Toluene → tert-butyl (1R,3S,4S)-3-(hydroxymethyl)-2-azabicyclo[2.2.1]heptane-2-carboxylate
Reaction equation
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]Participants
7
Reactant 4
Product 1
Reagents, catalysts & solvents 2
Procedure
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.
Workup
- customto reach rt
- customthe layers are separated
- extractionthe aq. layer is extracted three times with EtOAc (150 mL each)
- washThe combined organic layers are washed with aq. NaOH solution (1.0M) and brine
- dry with materialdried over Na2SO4
- concentrationconcentrated in vacuo
Sources & evidence
- ORD record
- ord-b2ce05038b2d4ac8b03cfccf3bfcfb4d
- Source dataset
- uspto-grants-2012_08
- Patent number
- US08236801B2
Reaction notes
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