Reaction #1256757

Reaction equation

2-Amino-5-methylbenzoic acid

pyridine

chloroformate

Methyl chloroformate

→

solid

Yield 31.0%

2-Hexadecyloxy-6-methyl-4H-3,1-benzoxazin-4-one

Yield 31.0%

Solvents

pentane

ethyl acetate

Conditions

Workup

1. 1
   Otherprepared above
2. 2
   workup.WAITthe mixture was left
3. 3
   workup.STIRRINGto stir at ambient temperature overnight
4. 4
   Washwashed with water (15 ml) and 10% aqueous citric acid (20 ml)
5. 5
   ExtractionThe combined aqueous phases were extracted with ethyl acetate (20 ml)
6. 6
   Washwashed with water (20 ml) and brine (20 ml)
7. 7
   Concentrationthen concentrated
8. 8
   Otherto give a solid
9. 9
   Filtrationfiltered
10. 10
    Filtrationfiltered
11. 11
    Otherpurified by flash chromatography on silica (1.5% diisopropylethylamine in dichloromethane)

Procedure

2-Amino-5-methylbenzoic acid (2.71 g, 17.9 mmol, 0.87 eq.) was dissolved in pyridine (24 ml) and added to the chloroformate solution prepared above. The mixture was stirred at room temperature for 1.75 hours. Methyl chloroformate (13.6 ml, 176 mmol, 8.5 eq) was added slowly, then the mixture was left to stir at ambient temperature overnight. The mixture was diluted with ethyl acetate (20 ml) and washed with water (15 ml) and 10% aqueous citric acid (20 ml). The combined aqueous phases were extracted with ethyl acetate (20 ml). The organic extracts were combined and washed with water (20 ml) and brine (20 ml) then concentrated to give a solid. This was slurried in pentane (5 ml), filtered, then slurried in acetonitrile (5 ml), filtered and purified by flash chromatography on silica (1.5% diisopropylethylamine in dichloromethane) to give a white solid (2.51 g, 31%) δH (400 MHz, CDCl3) 0.87 (3H, t, J 6.8, CH2CH3), 1.24-1.45 (26H, m, 13×CH2), 1.75-1.83 (2H, m, OCH2CH2), 2.41 (3H, s, ArCH3), 4.41 (2H, t, J 6.7, OCH2), 7.30 (1H, d, J 8.3, ArH), 7.51 (1H, dd, J 8.5, 2.0, ArH), 7.90 (1H, d, J 1.1, ArH); m/z (ES+) 402 (MH+); MPt. 72-73° C.

Source