Piperidine → HCID 89580877, compound

HRID 1501164Notes

Reaction equation

HRID 1501164 reaction equation
[CH:1]([C:3]1[CH:12]=[CH:11][C:6]([C:7]([O:9][CH3:10])=[O:8])=[C:5]([CH3:13])[CH:4]=1)=O.[NH:14]1[CH2:19][CH2:18][CH2:17][CH2:16][CH2:15]1.C([BH3-])#N.[Na+]>CO.C(O)(=O)C>[CH3:13][C:5]1[CH:4]=[C:3]([CH2:1][N:14]2[CH2:19][CH2:18][CH2:17][CH2:16][CH2:15]2)[CH:12]=[CH:11][C:6]=1[C:7]([O:9][CH3:10])=[O:8]

Participants

6

Reactant 3

HCID 8082PiperidineHCID 5003444Sodium cyanoborohydrideHCID 20134203Methyl 4-formyl-2-methylbenzoate

Product 1

HCID 89580877HCID 89580877, compoundYield 73.5%

Reagents, catalysts & solvents 2

HCID 176Acetic AcidCatalystHCID 887MethanolSolvent

Procedure

To a solution of methyl 4-formyl-2-methylbenzoate (300 mg, 1.7 mmol) and piperidine (92 mg, 1.1 mmol) in methanol (50 mL) was added acetic acid (1 drop) followed by sodium cyanoborohydride (221 mg, 3.5 mmol). The mixture was stirred at room temperature for 24 hours. The mixture was filtered, acidified with concentrated hydrochloride acid (1 mL) and concentrated in vacuo. To the residue, water (50 mL) was added. The mixture was extracted with dichloromethane (50 mL). The combined organic phase was separated, dried by sodium sulfate, filtered and concentrated to give a residue. The residue was purified by column chromatography (silica gel, petroleum ether/ethyl acetate=4:1, 1% NH3) to give methyl 2-methyl-4-(piperidin-1-ylmethyl)benzoate as a yellow oil (200 mg, 60%). LRMS (M+H+) m/z: calcd 247.16. found 247. 1H NMR (300 MHz, CDCl3): δ 7.73 (d, J=8.7 Hz, 1H), 7.52-7.50 (m, 2H), 3.91 (s, 3H), 3.62 (s, 2H), 2.52 (s, 3H), 2.32-2.24 (m, 4H), 1.47-1.44 (m, 6H).

Workup

  1. filtrationThe mixture was filtered
  2. concentrationconcentrated in vacuo
  3. additionTo the residue, water (50 mL) was added
  4. extractionThe mixture was extracted with dichloromethane (50 mL)
  5. customThe combined organic phase was separated
  6. dry with materialdried by sodium sulfate
  7. filtrationfiltered
  8. concentrationconcentrated
  9. customto give a residue
  10. customThe residue was purified by column chromatography (silica gel, petroleum ether/ethyl acetate=4:1, 1% NH3)

Sources & evidence

ORD record
ord-18e5eef9552344338eb654b2a99cb5d3
Source dataset
uspto-grants-2015_12
Patent number
US09206128B2

Reaction notes

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