Acetaldehyde → HCID 67979996, compound

HRID 1622310Notes

Reaction equation

HRID 1622310 reaction equation
C(O[C:6]([N:8]1[CH2:13][CH2:12][C:11]([C:15]([N:17]2[CH2:26][CH2:25][C:24]3[C:19](=[CH:20][CH:21]=[C:22]([C:27]([O:29][CH3:30])=[O:28])[CH:23]=3)[CH2:18]2)=[O:16])([CH3:14])[CH2:10][CH2:9]1)=O)(C)(C)C.Cl.[CH:32](=O)C.[O-]S([O-])(=O)=O.[Mg+2].C([BH3-])#N.[Na+]>CO>[CH2:6]([N:8]1[CH2:9][CH2:10][C:11]([C:15]([N:17]2[CH2:26][CH2:25][C:24]3[C:19](=[CH:20][CH:21]=[C:22]([C:27]([O:29][CH3:30])=[O:28])[CH:23]=3)[CH2:18]2)=[O:16])([CH3:14])[CH2:12][CH2:13]1)[CH3:32]

Participants

7

Reactant 5

HCID 177AcetaldehydeHCID 313Hydrochloric AcidHCID 24083Sulfuric acid magnesium salt (1:1)HCID 5003444Sodium cyanoborohydrideHCID 67979956HCID 67979956, compound

Product 1

HCID 67979996HCID 67979996, compoundYield 22%

Reagents, catalysts & solvents 1

HCID 887MethanolSolvent

Procedure

A solution of methyl 2-{[1-(tert-butoxycarbonyl)-4-methylpiperidin-4-yl]carbonyl}-1,2,3,4-tetrahydroisoquinoline-6-carboxylate.[HCl] (0.260 g, 0.737 mmol) in MeOH (8.0 mL) was treated with acetaldehyde (0.414 g, 7.37 mmol) and MgSO4 (excess). The reaction mixture was stirred at rt for 1 h, and sodium cyanoborohydride (93 mg, 1.47 mmol) was added in portions. The resulting mixture was stirred for 3 h at rt and then filtered to remove the MgSO4. The filtrate was washed with water and brine, dried over Na2SO4, filtered and concentrated. The resulting residue was purified by column chromatography (SiO2, 0-20% MeOH in DCM) to give methyl 2-[(1-ethyl-4-methylpiperidin-4-yl)carbonyl]-1,2,3,4-tetrahydroisoquinoline-6-carboxylate (55 mg, 22%). LC-MS: (FA) ES+ 345; 1H NMR (400 MHz, CDCl3) δ 7.86-7.80 (m, 2H), 7.18 (d, J=7.9 Hz, 1H), 4.78 (s, 2H), 3.89 (s, 3H), 3.88-3.83 (m, 2H), 2.91 (t, J=5.5 Hz, 2H), 2.77-2.67 (m, 2H), 2.42 (q, J=7.2 Hz, 2H), 2.36-2.20 (m, 4H), 1.75-1.65 (m, 2H), 1.30 (s, 3H), 1.09 (t, J=7.2 Hz, 3H).

Workup

  1. stirringThe resulting mixture was stirred for 3 h at rt
  2. filtrationfiltered
  3. customto remove the MgSO4
  4. washThe filtrate was washed with water and brine
  5. dry with materialdried over Na2SO4
  6. filtrationfiltered
  7. concentrationconcentrated
  8. customThe resulting residue was purified by column chromatography (SiO2, 0-20% MeOH in DCM)

Sources & evidence

ORD record
ord-47120239d9794948996d6b5b888f269a
Source dataset
uspto-grants-2014_07
Patent number
US08778931B2

Reaction notes

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