Acetaldehyde → Methyl 3-{[(2R,6R)-1-benzyl-2,6-dimethylpiperidin-4-yl](ethyl)amino}-5-fluoro-2-methylbenzoate

HRID 2208678Notes

Reaction equation

HRID 2208678 reaction equation
[CH2:1]([N:8]1[C@H:13]([CH3:14])[CH2:12][CH:11]([NH:15][C:16]2[C:17]([CH3:27])=[C:18]([CH:23]=[C:24]([F:26])[CH:25]=2)[C:19]([O:21][CH3:22])=[O:20])[CH2:10][C@H:9]1[CH3:28])[C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][CH:3]=1.[CH:29](=O)[CH3:30].C(O[BH-](OC(=O)C)OC(=O)C)(=O)C.[Na+]>ClCCl.C(O)(=O)C>[CH2:1]([N:8]1[C@H:13]([CH3:14])[CH2:12][CH:11]([N:15]([CH2:29][CH3:30])[C:16]2[C:17]([CH3:27])=[C:18]([CH:23]=[C:24]([F:26])[CH:25]=2)[C:19]([O:21][CH3:22])=[O:20])[CH2:10][C@H:9]1[CH3:28])[C:2]1[CH:3]=[CH:4][CH:5]=[CH:6][CH:7]=1

Participants

6

Reactant 3

HCID 177AcetaldehydeHCID 5049666Sodium triacetoxyborohydrideHCID 70873973Methyl 3-{[(2R,6R)-1-benzyl-2,6-dimethylpiperidin-4-yl]amino}-5-fluoro-2-methylbenzoate

Product 1

HCID 86719535Methyl 3-{[(2R,6R)-1-benzyl-2,6-dimethylpiperidin-4-yl](ethyl)amino}-5-fluoro-2-methylbenzoateYield 96%

Reagents, catalysts & solvents 2

HCID 176Acetic AcidSolventHCID 6344DichloromethaneSolvent

Procedure

To a stirred solution of methyl 3-{[(2R,6R)-1-benzyl-2,6-dimethylpiperidin-4-yl]amino}-5-fluoro-2-methylbenzoate (269 mg, 0.701 mmol) in dichloromethane (5 mL) and acetic acid (500 uL) was added acetaldehyde (124 mg, 2.80 mmol) and sodium triacetoxyborohydride (469 mg, 2.10 mmol) at 0° C. The reaction mixture was stirred at rt for 12 hours. Then the reaction mixture was quenched with aq. NaHCO3 until pH8-9. The content was extracted with ethylacetate. The organic layer was dried over MgSO4 and filtered. The filtrate was concentrated in vacuo. The residue was purified by silica gel column chromatography (NH—SiO2; heptane/ethylacetate=5/1) to give the titled compound as a light yellow oil (277 mg, 96% yield). 1HNMR (400 MHz, CDCl3) δppm; 7.19-7.36 (m, 6H), 6.97 (dd, J=2.4, 10.4 Hz, 1H), 3.89 (s, 3H), 3.86 (d, J=10.4 Hz, 1H), 3.39 (d, J=10.4 Hz, 1H), 3.02-3.10 (m, 4H), 2.74-2.80 (m, 1H), 2.43 (s, 3H), 1.74-1.82 (m, 1H), 1.51-1.63 (m, 2H), 1.32-1.40 (m, 1H), 1.05 (d, J=6.4 Hz, 3H), 0.93 (d, J=7.2 Hz, 3H), 0.86 (t, J=6.8 Hz, 3H); MS (ES) [M+H] 413.0.

Workup

  1. customThen the reaction mixture was quenched with aq. NaHCO3 until pH8-9
  2. extractionThe content was extracted with ethylacetate
  3. dry with materialThe organic layer was dried over MgSO4
  4. filtrationfiltered
  5. concentrationThe filtrate was concentrated in vacuo
  6. customThe residue was purified by silica gel column chromatography (NH—SiO2; heptane/ethylacetate=5/1)

Sources & evidence

ORD record
ord-5f22f155775c4086a722187917e968f5
Source dataset
uspto-grants-2016_06
Patent number
US09376422B2

Reaction notes

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