Ethanol → N-(1-(3,3-Dimethylbutyl)piperidin-4-yl)-N-((4-methylphenyl)methyl)-4-methoxyphenylacetamide

HRID 354111Notes

Reaction equation

HRID 354111 reaction equation
[CH3:1][C:2]1[CH:7]=[CH:6][C:5]([CH2:8][N:9]([CH:21]2[CH2:26][CH2:25][N:24]([C:27](OC(C)(C)C)=O)[CH2:23][CH2:22]2)[C:10](=[O:20])[CH2:11][C:12]2[CH:17]=CC(OC)=[CH:14][CH:13]=2)=[CH:4][CH:3]=1.[CH3:34][C:35]([CH3:40])([CH3:39])[CH2:36]C=O.[BH4-].[C:42](OC(=O)C)(=O)C.[CH2:49]([OH:51])[CH3:50]>>[CH3:34][C:35]([CH3:40])([CH3:39])[CH2:36][CH2:27][N:24]1[CH2:23][CH2:22][CH:21]([N:9]([CH2:8][C:5]2[CH:4]=[CH:3][C:2]([CH3:1])=[CH:7][CH:6]=2)[C:10](=[O:20])[CH2:11][C:12]2[CH:13]=[CH:14][C:49]([O:51][CH3:42])=[CH:50][CH:17]=2)[CH2:26][CH2:25]1

Participants

6

Reactant 5

HCID 702EthanolHCID 7918Acetic AnhydrideHCID 28123BorohydrideHCID 763353,3-DimethylbutanalHCID 12146688N-((4-methylphenyl)methyl)-N-(1-(tert-butyloxycarbonyl)piperidin-4-yl)-4-methoxyphenylacetamide

Product 1

HCID 12146689N-(1-(3,3-Dimethylbutyl)piperidin-4-yl)-N-((4-methylphenyl)methyl)-4-methoxyphenylacetamide

Procedure

The product from example 13 above (20 mg, 0.06 mmol) was dissolved in abs. ethanol (2 ml). 3,3-Dimethylbutyraldehyde (0.143 ml, 1.1 mmol) was added followed by solid-supported borohydride (150 mg, 2.5 mmol/g resin; Aldrich 32,864-2). The mixture was shaken at room temperature. After 48 h, the resin was filtered off and acetic anhydride (0.02 ml, 0.2 mmol) was added to the organic solution. After 24 h, the mixture was concentrated and redissolved in methanol (2 ml). The solution was added on to a column carrying strongly acidic cation exchange resin (0.3 mmol/g resin), which was washed with methanol (3×6 ml), and eluted with 10% NH3 in methanol, and concentrated to give the title compound. Yield: 26 mg; 13C-NMR (CD3OD, rotamers): δ 19.9, 27.4, 28.4, 28.8, 29.2, 29.3, 38.3, 38.4, 40.2, 40.3, 44.3, 52.0, 52.3, 52.4, 53.9, 54.6, 54.9, 114.0, 114.1, 126.0, 126.8, 127.0, 127.3, 128.8, 129.4, 129.8, 129.9, 135.0, 136.1, 136.3, 137.1, 158.96, 159.05, 173.2, 173.8.

Workup

  1. filtrationthe resin was filtered off
  2. waitAfter 24 h
  3. concentrationthe mixture was concentrated
  4. dissolutionredissolved in methanol (2 ml)
  5. additionThe solution was added on to a column
  6. washwas washed with methanol (3×6 ml)
  7. washeluted with 10% NH3 in methanol
  8. concentrationconcentrated

Sources & evidence

ORD record
ord-1480045db4ac42b7b6ab3a5b5f12ace4
Source dataset
uspto-grants-2004_06
Patent number
US06756393B2

Reaction notes

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