Dimethyl Carbonate → 2-Methyl-4-(2-propen-1-yloxy)benzoic acid

Temperature

-75 °C

To a solution of 4-allyloxy-1-bromo-2-methyl-benzene (10.87 g, 47.9 mmol) in THF (125 mL), a solution of n-butyl lithium (45 mL, 1.5 M in diethyl ether) is added at −75° C. The mixture is stirred at −75° C. for 30 min before it is transferred via a double-tip needle into a cooled (0° C.) solution of dimethylcarbonate (12.93 g, 144 mmol) in THF (45 mL). The mixture is stirred at 0° C. for 2 h, then at rt for 20 h before the solvents are removed in vacuo. The remaining oil is evaporated twice from ethanol (100 mL) before it is dissolved in 2 M aq. LiOH solution (75 mL) and ethanol (100 mL). The mixture is stirred at rt for 2 days and at 60° C. for 1 h. The org. solvent is evaporated and the remaining solution is diluted with 0.5 M aq. NaOH solution and extracted with diethyl ether (100 mL). The org. extract is washed with 1 M aq. NaOH solution (150 mL). The combined basic aq. extracts are washed with diethyl ether (100 mL), acidified with 25% aq. HCl and extracted with DCM (2×100 mL). The DCM extracts are combined, dried over MgSO4, filtered, concentrated and dried under high vacuum to give 4-allyloxy-2-methyl-benzoic acid (5.83 g) as an orange solid; LC-MS: tR=0.87 min; [M+1]+=not detectable; 1H NMR (CDCl3): δ 2.66 (s, 3H), 4.62 (dt, J=5.3, 1.5 Hz, 2H), 5.34 (dq, J=10.5, 1.5 Hz, 1H), 5.45 (dq, J=17.1, 1.5 Hz, 1H), 6.03-6.13 (m, 1H), 6.79-6.83 (m, 2H), 8.08 (d, J=9.5 Hz, 1H).

1. stirringThe mixture is stirred at 0° C. for 2 h
2. customat rt for 20 h before the solvents are removed in vacuo
3. customThe remaining oil is evaporated twice from ethanol (100 mL) before it
4. dissolutionis dissolved in 2 M aq. LiOH solution (75 mL)
5. stirringThe mixture is stirred at rt for 2 days and at 60° C. for 1 h
6. customsolvent is evaporated
7. additionthe remaining solution is diluted with 0.5 M aq. NaOH solution
8. extractionextracted with diethyl ether (100 mL)
9. extractionextract
10. washis washed with 1 M aq. NaOH solution (150 mL)
11. washThe combined basic aq. extracts are washed with diethyl ether (100 mL)
12. extractionextracted with DCM (2×100 mL)
13. dry with materialdried over MgSO4
14. filtrationfiltered
15. concentrationconcentrated
16. customdried under high vacuum

ORD record

ord-35ba9f9517bd4cbfa385e147741679a2

Source dataset

uspto-grants-2013_11

DOI

10.6084/m9.figshare.5104873.v1

Patent number

US08592460B2