Methanol → HCID 67268396, compound

Temperature

50 °C

4-(Benzyloxycarbonyl)morpholine-3-carboxylic acid (crude material, 21.2 g, about 75 mmol) was dissolved in methanol (250 ml). Sulfuric acid (12.01 ml, 225 mmol) was added slowly with vigorous stirring. An exotherm was noticed and the temperature rose to 34° C. after the addition. Once the addition was complete, reaction solution was heated to 50° C. for 18 hours. The reaction mixture was cooled to room temperature and concentrated to remove most of the methanol. EtOAc (500 ml) was added and the organic solution was washed with water (150 ml), saturated sodium bicarbonate solution (100 ml) and water (150 ml). The organic solution was then concentrated to give a residue which was purified by silica gel column (330 g silica gel, hexanes/EtOAc 5:1) to afford 15.9 gram of 4-benzyl 3-methyl morpholine-3,4-dicarboxylate as clear oil. 1H NMR (400 MHz, CDCl3) δ=3.28-3.57 (m, 2H), 3.67 (m, 1H), 3.57-3.96 (m, 5H), 4.4 (dd, 1H), 4.61 (dd, 1H), 5.19 (m, 2H), 7.32-7.4 (m, 5H)

1. customrose to 34° C.
2. additionafter the addition
3. additionOnce the addition
4. customreaction solution
5. temperatureThe reaction mixture was cooled to room temperature
6. concentrationconcentrated
7. customto remove most of the methanol
8. additionEtOAc (500 ml) was added
9. washthe organic solution was washed with water (150 ml), saturated sodium bicarbonate solution (100 ml) and water (150 ml)
10. concentrationThe organic solution was then concentrated
11. customto give a residue which
12. customwas purified by silica gel column (330 g silica gel, hexanes/EtOAc 5:1)

ORD record

ord-5d48be950ba643fb90dc000452382d35

Source dataset

uspto-grants-2012_09

DOI

10.6084/m9.figshare.5104873.v1

Patent number

US08268819B2