Acetone → HCID 591057, compound

Temperature

0 °C

A 5 L three neck flask was charged with 562 g (4.35 mol) of 3-amino-2-hydroxymethylthiophene (Step 1). It was suspended in 3 L of EtOAc and cooled to 0° C. (ice bath). 2.0 Kg of MnO2 (23.0 mol.; 5.3 eq) was added portionwise (250 g) over 45 min. with mechanical stirring. Upon addition of the MnO2 the reaction temperature rose to 20° C. The reaction mixture was stirred at 20° C. for 1 h until total consumption of starting material by TLC (Hex/EtOAc 1:1). The solids were removed by filtration over 2 L of celite and washed 3 times with 2 L of EtOAc/THF (1:1). The combined filtrates were evaporated to dryness to give a black residue. The residue was dissolved in 1.28 L of acetone (17.4 mol, 4.0 eq) and transferred to a 10 L three neck flask charged with 3 L of 2.5% NaOH. The mixture was then stirred at 70° C. for 1 h. The two phase mixture was cooled to 20° C., 2 L of ether was added and stirred for 15 min. The phases were separated and the aqueous phase was backwashed with 2×1 L of ether. The organic fractions were combined, washed with 2 L of brine and evaporated to dryness to give a black oil. The latter was distilled under vacuum (@70° C., 0.3 mm Hg) to give the title compound: 492 g; 76%.

1. customrose to 20° C
2. customThe solids were removed by filtration over 2 L of celite
3. washwashed 3 times with 2 L of EtOAc/THF (1:1)
4. customThe combined filtrates were evaporated to dryness
5. customto give a black residue
6. temperatureThe two phase mixture was cooled to 20° C.
7. stirringstirred for 15 min
8. customThe phases were separated
9. washwashed with 2 L of brine
10. customevaporated to dryness
11. customto give a black oil
12. distillationThe latter was distilled under vacuum (@70° C., 0.3 mm Hg)

ORD record

ord-fd63e235633d415d82c1ee779948b820

Source dataset

uspto-grants-1995_12

DOI

10.6084/m9.figshare.5104873.v1

Patent number

US05472964