6-Methoxy-alpha-tetralone → 1-(Aminomethyl)-6-methoxy-1,2,3,4-tetrahydronaphthalen-1-ol
Reaction equation
[Si]([C:5]#[N:6])(C)(C)C.[CH3:7][O:8][C:9]1[CH:10]=[C:11]2[C:16](=[CH:17][CH:18]=1)[C:15](=[O:19])[CH2:14][CH2:13][CH2:12]2.[H-].[Al+3].[Li+].[H-].[H-].[H-].[OH-].[Na+]>C1(C)C=CC=CC=1.C1COCC1.CCOC(C)=O.[I-].[Zn+2].[I-].O>[NH2:6][CH2:5][C:15]1([OH:19])[C:16]2[C:11](=[CH:10][C:9]([O:8][CH3:7])=[CH:18][CH:17]=2)[CH2:12][CH2:13][CH2:14]1Participants
Reactant 4
Product 1
Reagents, catalysts & solvents 5
Conditions
- Temperature
- 60 °C
Procedure
TMS-cyanide (8.52 mL, 68.1 mmol) was added to a solution of 6-methoxy-1-tetralone (6.0 g, 34 mmol) in toluene (50 mL). A trace amount (−20 mg) of zinc iodide was added, and the reaction was stirred at 60° C. for 16 hours. The solution was cooled to rt and diluted with THF (30 mL). This was added to a mixture of lithium aluminum hydride (2.58 g) in THF (50 mL), and the reaction mixture was heated at 42° C. for 2 h. The reaction was cooled to rt. EtOAc (10 mL) was slowly added, and the reaction stirred 30 min. Water (2 mL) and then 5N NaOH (1 mL) were slowly added, and the reaction stirred 1 h. The reaction mixture was diluted with EtOAc (100 mL), dried (MgSO4), and filtered through Celite. Purification by silica gel chromatography (10-20% MeOH/DCM) gave 4.82 g of 1-(aminomethyl)-6-methoxy-1,2,3,4-tetrahydronaphthalen-1-ol as a clear oil.
Workup
- temperatureThe solution was cooled to rt
- temperaturethe reaction mixture was heated at 42° C. for 2 h
- temperatureThe reaction was cooled to rt
- stirringthe reaction stirred 30 min
- stirringthe reaction stirred 1 h
- dry with materialdried (MgSO4)
- filtrationfiltered through Celite
- customPurification by silica gel chromatography (10-20% MeOH/DCM)
Sources & evidence
- ORD record
- ord-8b377a9da5ad4cf784365e0a2aaef1d6
- Source dataset
- uspto-grants-2015_07
- Patent number
- US09085534B2
Reaction notes
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