Acetic Acid → HCID 16744634, compound

Temperature

5 °C

At 0-10° C., 61.3 g of methyl 3-mercaptopropionate (3, 0.5 mol, content: 98%) were added dropwise over 35 min to 90 g of a 30% solution of NaOMe in methanol (0.5 mol). After the addition, the mixture was stirred at 0-10° C. for a further 10 min and subsequently, at 0-5° C., 63.2 g of methyl 2-chloropropionate (4, 0.5 mol, content: 97%) were metered in over 50 min. The reaction mixture was stirred at 0-5° C. for a further 30 min, before 500 ml of xylene were added. Subsequently, the methanol was substantially distilled off. 99 g of a 30% solution of NaOMe in methanol (0.55 mol) were added dropwise at approx. 90° C. over 75 min to the resulting suspension, and methanol continued to be distilled off at the same time. The reaction mixture was then cooled to 80° C. under argon before 33 g of acetic acid (0.55 mol) were metered in. On completion of addition, 500 ml of water were added at 70° C. and the mixture was subsequently cooled to room temperature. After the separation of the phases, the aqueous phase was reextracted once more with 250 ml of xylene and the combined organic phases were subsequently washed once more with 100 ml of water. The organic phase was dried (Na2SO4) and concentrated under reduced pressure. The residue was admixed with 830 ml of methanol and 94.6 g of ammonium formate (1.5 mol) and then heated to reflux. After 12 h under reflux, the workup was effected by substantial concentration. The residue was taken up in 500 ml of water and extracted three times with 200 ml each time of dichloromethane. The combined organic phases were dried (Na2SO4). After the solvent had been distilled off under reduced pressure, 81 g of methyl 4-amino-5-methyl-2,5-dihydrothiophene-3-carboxylate (2) were obtained (68% of theory over all stages, content: 72.5%).

1. additionAfter the addition
2. customat 0-5° C.
3. customwere metered in over 50 min
4. additionwere added
5. distillationSubsequently, the methanol was substantially distilled off
6. distillationto be distilled off at the same time
7. additionwere added at 70° C.
8. temperaturethe mixture was subsequently cooled to room temperature
9. customAfter the separation of the phases
10. washthe combined organic phases were subsequently washed once more with 100 ml of water
11. dry with materialThe organic phase was dried (Na2SO4)
12. concentrationconcentrated under reduced pressure
13. temperatureheated to reflux
14. temperatureAfter 12 h under reflux
15. concentrationthe workup was effected by substantial concentration
16. extractionextracted three times with 200 ml each time of dichloromethane
17. dry with materialThe combined organic phases were dried (Na2SO4)
18. distillationAfter the solvent had been distilled off under reduced pressure

ORD record

ord-868370491f9e446385b94c4cf862ec93

Source dataset

uspto-grants-2011_04

DOI

10.6084/m9.figshare.5104873.v1

Patent number

US07923571B2