Acetaldehyde → Methyl 3-{[(2R*,6S*)-1-benzyl-2,6-dimethylpiperidin-4-yl](ethyl)amino}-2-methyl-5-(trifluoromethyl)benzoate

HRID 2208673Notes

Reaction equation

HRID 2208673 reaction equation
[CH2:1]([N:8]1[C@@H:13]([CH3:14])[CH2:12][CH:11]([NH:15][C:16]2[C:17]([CH3:30])=[C:18]([CH:23]=[C:24]([C:26]([F:29])([F:28])[F:27])[CH:25]=2)[C:19]([O:21][CH3:22])=[O:20])[CH2:10][C@H:9]1[CH3:31])[C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][CH:3]=1.[CH:32](=O)[CH3:33].C(O[BH-](OC(=O)C)OC(=O)C)(=O)C.[Na+]>C(Cl)(Cl)Cl.C(O)(=O)C>[CH2:1]([N:8]1[C@@H:13]([CH3:14])[CH2:12][CH:11]([N:15]([CH2:32][CH3:33])[C:16]2[C:17]([CH3:30])=[C:18]([CH:23]=[C:24]([C:26]([F:29])([F:27])[F:28])[CH:25]=2)[C:19]([O:21][CH3:22])=[O:20])[CH2:10][C@H:9]1[CH3:31])[C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][CH:3]=1

Participants

6

Reactant 3

HCID 177AcetaldehydeHCID 5049666Sodium triacetoxyborohydrideHCID 70874011Methyl 3-{[(2R*,6S*)-1-benzyl-2,6-dimethylpiperidin-4-yl]amino}-2-methyl-5-(trifluoromethyl)benzoate

Product 1

HCID 86719533Methyl 3-{[(2R*,6S*)-1-benzyl-2,6-dimethylpiperidin-4-yl](ethyl)amino}-2-methyl-5-(trifluoromethyl)benzoateYield 44%

Reagents, catalysts & solvents 2

HCID 176Acetic AcidSolventHCID 6212ChloroformSolvent

Conditions

Temperature
0 °C

Procedure

To a stirred solution of methyl 3-{[(2R,6S)-1-benzyl-2,6-dimethylpiperidin-4-yl]amino}-2-methyl-5-(trifluoromethyl)benzoate (223 mg, 0.513 mmol) in chloroform (4 mL) and acetic acid (500 uL) was added acetaldehyde (1.0 ml) and stirred for 30 min at 0° C. Then sodium triacetoxyborohydride (343 mg, 1.54 mmol) was added to the reaction mixture at 0° C. The reaction mixture was stirred at 23° C. for 4 hours. Then the reaction mixture was quenched with aq. NaHCO3 until pH8-9. The content was extracted with ethylacetate. The organic layer was washed with brine. The organic layer was dried over MgSO4 and filtered. The filtrate was concentrated in vacuo. The residue was purified by silica gel column chromatography (heptane/ethylacetate=4/1 to 1/2) to give the titled compound as a colorless oil. (105.5 mg, 44% yield). MS (ES) [M+H] 463.3.

Workup

  1. stirringThe reaction mixture was stirred at 23° C. for 4 hours
  2. customThen the reaction mixture was quenched with aq. NaHCO3 until pH8-9
  3. extractionThe content was extracted with ethylacetate
  4. washThe organic layer was washed with brine
  5. dry with materialThe organic layer was dried over MgSO4
  6. filtrationfiltered
  7. concentrationThe filtrate was concentrated in vacuo
  8. customThe residue was purified by silica gel column chromatography (heptane/ethylacetate=4/1 to 1/2)

Sources & evidence

ORD record
ord-922218ab936f46a9bcd54ebedef3be6c
Source dataset
uspto-grants-2016_06
Patent number
US09376422B2

Reaction notes

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