Acetic Acid → 2-Ethyl-1,2,3,4-tetrahydroisoquinoline-7-carbonitrile

HRID 219571

Reaction equation

HRID 219571 reaction equation
[CH2:1]1[C:10]2[C:5](=[CH:6][CH:7]=[C:8]([C:11]#[N:12])[CH:9]=2)[CH2:4][CH2:3][NH:2]1.[CH:13](=O)[CH3:14].C(O)(=O)C.C([BH3-])#N.[Na+]>CO.C(Cl)Cl.O>[CH2:13]([N:2]1[CH2:3][CH2:4][C:5]2[C:10](=[CH:9][C:8]([C:11]#[N:12])=[CH:7][CH:6]=2)[CH2:1]1)[CH3:14]

Participants

8

Reactant 4

HCID 176Acetic AcidHCID 177AcetaldehydeHCID 5003444Sodium cyanoborohydrideHCID 101762437-Cyano-1,2,3,4-tetrahydroisoquinoline

Product 1

HCID 597463522-Ethyl-1,2,3,4-tetrahydroisoquinoline-7-carbonitrile

Reagents, catalysts & solvents 3

HCID 887MethanolSolventHCID 962WaterSolventHCID 6344DichloromethaneSolvent

Procedure

To a solution of 1,2,3,4-tetrahydroisoquinoline-7-carbonitrile (ABCR; 500 mg; 3.16 mmol) in MeOH (5 mL) at 0° C. was added acetaldehyde (0.51 mL, 8.91 mmol) and acetic acid (5 μL) and the resulting mixture was stirred for 1 hour. Sodium cyanoborohydride (218 mg; 3.47 mmol) was added and the mixture was stirred for 5 hours and diluted with DCM (100 mL) and water (20 mL). The aqueous layer was extracted with DCM (3×20 mL), the combined organics were dried (MgSO4) and the solvent was removed in vacuo. The residue was purified by flash chromatography on a Biotage 25+M column, eluting with petrol containing increasing amounts of EtOAc to give the title compound as a brown oil. 1H NMR: (CDCl3, 400 MHz) δ 7.39 (1H, d, J=8.0 Hz), 7.33 (1H, s), 7.19 (1H, d, J=8.0 Hz), 3.62 (2H, s), 2.99-2.90 (2H, m), 2.77-2.70 (2H, m), 2.66-2.54 (2H, m), 1.19 (3H, t, J=7.2 Hz).

Workup

  1. stirringthe mixture was stirred for 5 hours
  2. extractionThe aqueous layer was extracted with DCM (3×20 mL)
  3. dry with materialthe combined organics were dried (MgSO4)
  4. customthe solvent was removed in vacuo
  5. customThe residue was purified by flash chromatography on a Biotage 25+M column
  6. washeluting with petrol containing
  7. temperatureincreasing amounts of EtOAc

Sources & evidence

ORD record
ord-9004fde4d0c04ff7988142e08b0c501d
Source dataset
uspto-grants-2012_06
Patent number
US08202856B2

Linked notes

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