Formaldehyde → 4-Benzyloxy-1-[2-(2-methyl-1,2,3,4-tetrahydro-isoquinolin-7-yl)-ethyl]-1H-pyridin-2-one

HRID 564183Notes

Reaction equation

HRID 564183 reaction equation
[CH2:1]([O:8][C:9]1[CH:14]=[CH:13][N:12]([CH2:15][CH2:16][C:17]2[CH:26]=[C:25]3[C:20]([CH2:21][CH2:22][NH:23][CH2:24]3)=[CH:19][CH:18]=2)[C:11](=[O:27])[CH:10]=1)[C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][CH:3]=1.C=O.[C:30](O[BH-](OC(=O)C)OC(=O)C)(=O)C.[Na+].C([O-])([O-])=O.[Na+].[Na+]>C1COCC1.C(O)(=O)C>[CH2:1]([O:8][C:9]1[CH:14]=[CH:13][N:12]([CH2:15][CH2:16][C:17]2[CH:26]=[C:25]3[C:20]([CH2:21][CH2:22][N:23]([CH3:30])[CH2:24]3)=[CH:19][CH:18]=2)[C:11](=[O:27])[CH:10]=1)[C:2]1[CH:3]=[CH:4][CH:5]=[CH:6][CH:7]=1

Participants

7

Reactant 4

HCID 712Formaldehyde3×HCID 10340Sodium CarbonateHCID 5049666Sodium triacetoxyborohydride3×HCID 580427534-Benzyloxy-1-[2-(1,2,3,4-tetrahydro-isoquinolin-7-yl)-ethyl]-1H-pyridin-2-one

Product 1

HCID 580427684-Benzyloxy-1-[2-(2-methyl-1,2,3,4-tetrahydro-isoquinolin-7-yl)-ethyl]-1H-pyridin-2-one

Reagents, catalysts & solvents 2

HCID 176Acetic AcidCatalystHCID 8028TetrahydrofuranSolvent

Procedure

To 150 mg (0.42 mmol) 4-benzyloxy-1-[2-(1,2,3,4-tetrahydro-isoquinolin-7-yl)-ethyl]-1H-pyridin-2-one (example 24.2) in 5.0 mL THF is added 68 μL (0.83 mmol) aqueous 37% formaldehyde solution. The mixture is acidified with 3 drops of acetic acid and then 97 mg (0.46 mmol) sodium triacetoxy-borohydride is added. The reaction mixture is stirred 2 h at RT and additional 68 μL (0.83 mmol) aqueous 37% formaldehyde solution and 97 mg (0.46 mmol) sodium triacetoxy-borohydride are added. The reaction mixture is stirred overnight and additional 68 μL (0.83 mmol) aqueous 37% formaldehyde solution and 97 mg (0.46 mmol) sodium triacetoxy-borohydride is added and the reaction mixture is stirred additional 48 h at RT. The mixture is poured into aqueous 10% Na2CO3-solution, the layers are separated and the aqueous phase is extracted with DCM. The combined organic phase is washed a few times with water, dried over MgSO4, filtered and the solvent is evaporated. The residue is purified via reverse HPLC chromatography (Zorbax stable bond, C18; water (0.15% formic acid)/acetonitrile 95:5 to 5:95).

Workup

  1. stirringThe reaction mixture is stirred overnight
  2. stirringthe reaction mixture is stirred additional 48 h at RT
  3. customthe layers are separated
  4. extractionthe aqueous phase is extracted with DCM
  5. washThe combined organic phase is washed a few times with water
  6. dry with materialdried over MgSO4
  7. filtrationfiltered
  8. customthe solvent is evaporated
  9. customThe residue is purified via reverse HPLC chromatography (Zorbax stable bond, C18; water (0.15% formic acid)/acetonitrile 95:5 to 5:95)

Sources & evidence

ORD record
ord-8e4e077798f048f9abb67248bd2beae8
Source dataset
uspto-grants-2011_11
Patent number
US08067590B2

Reaction notes

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