Formaldehyde → 4-[(E)-2-[6-[2-[2-(2-fluoroethoxy)ethoxy]ethoxy]pyridin-3-yl]ethenyl]-N-methylaniline

HRID 77242Notes

Reaction equation

HRID 77242 reaction equation
[CH3:1][O-].[Na+].[F:4][CH2:5][CH2:6][O:7][CH2:8][CH2:9][O:10][CH2:11][CH2:12][O:13][C:14]1[CH:19]=[CH:18][C:17](/[CH:20]=[CH:21]/[C:22]2[CH:27]=[CH:26][C:25]([NH2:28])=[CH:24][CH:23]=2)=[CH:16][N:15]=1.C=O.[BH4-].[Na+]>CO.O.ClCCl>[F:4][CH2:5][CH2:6][O:7][CH2:8][CH2:9][O:10][CH2:11][CH2:12][O:13][C:14]1[CH:19]=[CH:18][C:17](/[CH:20]=[CH:21]/[C:22]2[CH:27]=[CH:26][C:25]([NH:28][CH3:1])=[CH:24][CH:23]=2)=[CH:16][N:15]=1

Participants

8

Reactant 4

HCID 712FormaldehydeHCID 4311764Sodium borohydrideHCID 10942334Sodium MethoxideHCID 86618271(E)-2-(2-(2-(2-fluoroethoxy)ethoxy)ethoxy)-5-(4-aminostyryl)pyridine

Product 1

HCID 573968654-[(E)-2-[6-[2-[2-(2-fluoroethoxy)ethoxy]ethoxy]pyridin-3-yl]ethenyl]-N-methylanilineYield 73%

Reagents, catalysts & solvents 3

HCID 887MethanolSolventHCID 962WaterSolventHCID 6344DichloromethaneSolvent

Conditions

Temperature
0 °C

Procedure

Sodium methoxide (1M in methanol, 0.23 ml) was added to a solution of compound 5 (15.8 mg, 0.046 mmol) in methanol (5 ml) followed by the addition of paraformaldehyde (6.6 mg, 0.23 mmol). The reaction mixture was refluxed for 1.5 hour then cooled to 0° C. with an ice bath. Sodium borohydride (10.4 mg, 0.27 mmol) was added with caution. The mixture was refluxed again for 1 hour and cooled down. Dichloromethane and water was added. Organic layer was separated, washed with brine, dried over anhydrous sodium sulfate and evaporated. The residue was purified by PTLC (3% MeOH in DCM as developing solvent) to give product 6 (12 mg, Yield: 73%): 1H NMR (200 MHz, CDCl3): δ.8.14 (1H, d, J=2.2 Hz), 7.76 (1H, d, d, J1=8.6 Hz, J2=2.4 Hz), 7.35 (2H, d, J=8.6 Hz), 6.92 (1H, d, J=16.4 Hz), 6.80 (1H, d, J=16.4 Hz), 6.76 (2H, d, J=8.6 Hz), 4.53 (2H, d, t, J1=47.6 Hz, J2=4.2 Hz), 4.49 (2H, t, J=4.8 Hz), 3.85 (3H, m), 3.70 (5H, m), 2.88 (3H, s). HRMS (EI) m/z calcd. for [C20H25FN2O3]+ 360.1849.

Workup

  1. temperatureThe reaction mixture was refluxed for 1.5 hour
  2. temperatureThe mixture was refluxed again for 1 hour
  3. temperaturecooled down
  4. customOrganic layer was separated
  5. washwashed with brine
  6. dry with materialdried over anhydrous sodium sulfate
  7. customevaporated
  8. customThe residue was purified by PTLC (3% MeOH in DCM as developing solvent)

Sources & evidence

ORD record
ord-3d94b5d8a8914550b944d3b07c18e775
Source dataset
uspto-grants-2014_09
Patent number
US08840866B2

Reaction notes

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