Formaldehyde → Methyl 5-[(4-[(4-butylphenyl)ethynyl]benzyl}(methyl)amino]-2-fluorobenzoate

HRID 551960Notes

Reaction equation

HRID 551960 reaction equation
[CH2:1]([C:5]1[CH:10]=[CH:9][C:8]([C:11]#[C:12][C:13]2[CH:31]=[CH:30][C:16]([CH2:17][NH:18][C:19]3[CH:20]=[CH:21][C:22]([F:29])=[C:23]([CH:28]=3)[C:24]([O:26][CH3:27])=[O:25])=[CH:15][CH:14]=2)=[CH:7][CH:6]=1)[CH2:2][CH2:3][CH3:4].[CH2:32]=O.[OH-].[Na+]>C(O)=O>[CH2:1]([C:5]1[CH:6]=[CH:7][C:8]([C:11]#[C:12][C:13]2[CH:14]=[CH:15][C:16]([CH2:17][N:18]([CH3:32])[C:19]3[CH:20]=[CH:21][C:22]([F:29])=[C:23]([CH:28]=3)[C:24]([O:26][CH3:27])=[O:25])=[CH:30][CH:31]=2)=[CH:9][CH:10]=1)[CH2:2][CH2:3][CH3:4]

Participants

5

Reactant 3

HCID 712FormaldehydeHCID 14798Sodium HydroxideHCID 11452740Methyl 5-({4-[(4-butylphenyl)ethynyl]benzyl}amino)-2-fluorobenzoate

Product 1

HCID 57554550Methyl 5-[(4-[(4-butylphenyl)ethynyl]benzyl}(methyl)amino]-2-fluorobenzoateYield 22.3%

Reagents, catalysts & solvents 1

HCID 284Formic AcidSolvent

Procedure

A solution of methyl 5-({4-[(4-butylphenyl)ethynyl]benzyl}amino)-2-fluorobenzoate (305 mg; 0.73 mmol), formaldehyde (Aldrich, 50 μl; 1.84 mmol) and formic acid (2.5 mL) was stirred under microwaves at 100° C. for 5 min. The reaction mixture was then poured into an aqueous solution of NaOH 1M and extracted twice with EtOAc. The combined organic layers were washed with brine, dried over magnesium sulfate, filtrated and concentrated. Purification of the crude (257 mg, yellow oil) by flash chromatography on silicagel afforded 70 mg of the title compound as a yellow powder. HPLC, Rt: 5.84. min (purity=100%). 1H NMR (CDCl3) δ: 7.4 (m, 4H), 7.3 (s, 1H), 7.2 (m, 4H), 6.9 (t, J=7.8 Hz, 1H), 6.75 (m, 1H), 4.4 (s, 2H), 2.92 (s, 3H), 2.5 (t, J=7.7 Hz, 2H), 1.5 (m, 2H), 1.25 (m, 2H), 0.8 (t, J=7.53 Hz, 3H).

Workup

  1. extractionextracted twice with EtOAc
  2. washThe combined organic layers were washed with brine
  3. dry with materialdried over magnesium sulfate
  4. filtrationfiltrated
  5. concentrationconcentrated
  6. customPurification of the crude (257 mg, yellow oil) by flash chromatography on silicagel

Sources & evidence

ORD record
ord-752b8109fa3748ae8a2565ee647ccc16
Source dataset
uspto-grants-2011_05
Patent number
US07947851B2

Reaction notes

Loading…