Acetic Acid → 2-(Cyclohexylmethyl)-4,4-dimethyl-7-nitro-1,2,3,4-tetrahydroisoquinoline

HRID 2370637Notes

Reaction equation

[B-]C#N.[Na+].[CH3:5][C:6]1([CH3:19])[C:15]2[C:10](=[CH:11][C:12]([N+:16]([O-:18])=[O:17])=[CH:13][CH:14]=2)[CH2:9][NH:8][CH2:7]1.C(O)(=O)C.[CH:24]1([CH:30]=O)[CH2:29][CH2:28][CH2:27][CH2:26][CH2:25]1.C(=O)(O)[O-].[Na+]>CO>[CH:24]1([CH2:30][N:8]2[CH2:7][C:6]([CH3:19])([CH3:5])[C:15]3[C:10](=[CH:11][C:12]([N+:16]([O-:18])=[O:17])=[CH:13][CH:14]=3)[CH2:9]2)[CH2:29][CH2:28][CH2:27][CH2:26][CH2:25]1

Participants

Conditions

Temperature: 35 °C

Procedure

Sodium cyanotrihydroborate (0.600 g, 9.55 mmol) was added to a solution of 4,4-dimethyl-7-nitro-1,2,3,4-tetrahydroisoquinoline (0.600 g, 2.91 mmol), acetic acid (0.210 mL, 3.66 mmol) and cyclohexanecarbaldehyde (0.4 g, 3.57 mmol) in methanol (40 mL). The reaction mixture was stirred at 35° C. for 16 hours. The reaction was neutralized with saturated sodium bicarbonate solution, and the mixture was concentrated under reduced pressure. The residue was diluted with water and extracted with ethyl acetate (3×50 mL). The combined organic layers were washed with brine, dried over Na2SO4, filtered, and concentrated. The crude product was purified with silica gel column chromatography (3% ethyl acetate/petroleum ether) to provide the title compound.

Workup

concentrationthe mixture was concentrated under reduced pressure
additionThe residue was diluted with water
extractionextracted with ethyl acetate (3×50 mL)
washThe combined organic layers were washed with brine
dry with materialdried over Na2SO4
filtrationfiltered
concentrationconcentrated
customThe crude product was purified with silica gel column chromatography (3% ethyl acetate/petroleum ether)

Sources & evidence

ORD record: ord-ee28d1c4a9b747f7a57b1316f97ad7f7
Source dataset: uspto-grants-2014_04
DOI: 10.6084/m9.figshare.5104873.v1
Patent number: US08710065B2

Reaction notes

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