Triethylamine → Methyl 3-{[isobutyl(methyl)amino]methyl}-5-methylbenzoate

HRID 14133Notes

Reaction equation

HRID 14133 reaction equation
O[CH2:2][C:3]1[CH:4]=[C:5]([CH:10]=[C:11]([CH3:13])[CH:12]=1)[C:6]([O:8][CH3:9])=[O:7].C(N(CC)CC)C.CS(Cl)(=O)=O.[CH3:26][NH:27][CH2:28][CH:29]([CH3:31])[CH3:30]>C(Cl)Cl>[CH2:28]([N:27]([CH2:2][C:3]1[CH:4]=[C:5]([CH:10]=[C:11]([CH3:13])[CH:12]=1)[C:6]([O:8][CH3:9])=[O:7])[CH3:26])[CH:29]([CH3:31])[CH3:30]

Participants

6

Reactant 4

HCID 8471TriethylamineHCID 12249N-MethylisobutylamineHCID 31297Methanesulfonyl chlorideHCID 21086184Methyl 3-(hydroxymethyl)-5-methylbenzoate

Product 1

HCID 21086186Methyl 3-{[isobutyl(methyl)amino]methyl}-5-methylbenzoate

Reagents, catalysts & solvents 1

HCID 6344DichloromethaneSolvent2×

Procedure

To an ice-cold, stirred solution of methyl 3-(hydroxymethyl)-5-methylbenzoate (200 mg, 1.1 mmol) in methylene chloride (2.2 mL) is added triethylamine (0.304 mL, 2.2 mmol) followed by methanesulfonyl chloride (0.116 mL, 1.5 mmol). The reaction mixture is stirred for 15 min and filtered. N-Methylisobutylamine (287 mg, 3.3 mmol) is added to the filtrate, and the reaction mixture is stirred at room temperature for 5 h. The reaction mixture is diluted with methylene chloride (10 mL), washed with 1 N hydrochloric acid, and saturated sodium bicarbonate, dried (magnesium sulfate), filtered, and concentrated under reduced pressure. Purification by flash column chromatography (silica, 15% ethyl acetate/hexanes) provides the title compound. 1H NMR (300 MHz, CDCl3) δ 7.77 (s, 1H), 7.73 (s, 1H), 7.36 (s, 1H), 3.90 (s, 3H), 3.44 (s, 2H), 2.38 (s, 3H), 2.14 (s, 3H), 2.10 (d, J=8 Hz, 2H), 1.81 (m, 1H), 0.90 (d, J=7 Hz, 6H).

Workup

  1. filtrationfiltered
  2. stirringthe reaction mixture is stirred at room temperature for 5 h
  3. washwashed with 1 N hydrochloric acid, and saturated sodium bicarbonate
  4. dry with materialdried (magnesium sulfate)
  5. filtrationfiltered
  6. concentrationconcentrated under reduced pressure
  7. customPurification by flash column chromatography (silica, 15% ethyl acetate/hexanes)

Sources & evidence

ORD record
ord-ebeebd16d2ba4b0ab5865ad9622d68d2
Source dataset
uspto-grants-2010_06
Patent number
US07727997B2

Reaction notes

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