Methanol → Methyl 3-hydroxy-2-methylbenzoate

Temperature

60 °C

3-Hydroxy-2-methylbenzoic acid (250 g, 1.32 mole) was added to methanol (2500 mL, 10×) in a jacketed bottom drop three neck flask under nitrogen. Sulfuric acid (48.3 g, 0.49 mole) was added to the above solution. The mixture was heated to 60° C. and stirred for 8 to 17 hours. Once conversion was >98%, the mixture was atmospherically distilled to 3× volume. The residue was cooled to 20° C. and slowly added to water (500 mL, 2×) over at least 30 minutes. Seeds (2 g, 0.01×) were added and the mixture was agitated at 20° C. for at least 1 hour. Water (1500 mL, 6×) was added at 20° C. over at least 3 hours and the mixture was agitated at 20° C. for at least one additional hour. The solid was filtered, and washed three times with 9:1 water:methanol (500 mL, 2× each) until pH≧3. The solid was dried under vacuum at 35 to 45° C. until KF≦0.1% to give methyl 3-hydroxy-2-methylbenzoate (235.3 g, 86% yield);

1. distillationthe mixture was atmospherically distilled to 3× volume
2. temperatureThe residue was cooled to 20° C.
3. additionslowly added to water (500 mL, 2×) over at least 30 minutes
4. additionSeeds (2 g, 0.01×) were added
5. stirringthe mixture was agitated at 20° C. for at least 1 hour
6. additionWater (1500 mL, 6×) was added at 20° C. over at least 3 hours
7. stirringthe mixture was agitated at 20° C. for at least one additional hour
8. filtrationThe solid was filtered
9. washwashed three times with 9:1 water
10. dry with materialThe solid was dried under vacuum at 35 to 45° C. until KF≦0.1%

ORD record

ord-5dec559aeb0a407d8f34773b79925a8d

Source dataset

uspto-grants-2016_04

DOI

10.6084/m9.figshare.5104873.v1

Patent number

US09309220B2