6-Methoxy-alpha-tetralone → 1-(Aminomethyl)-6-methoxy-1,2,3,4-tetrahydronaphthalen-1-ol

HRID 63075

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]1

Participants

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-060b901605a7488ead9bd01c7620fa71
Source dataset: uspto-grants-2016_09
DOI: 10.6084/m9.figshare.5104873.v1
Patent number: US09447045B2

Linked notes

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