Methyl iodide → HCID 67268388, compound

Temperature

-70 °C

4-Benzyl 3-methyl morpholine-3,4-dicarboxylate (13.98 g, 50.1 mmol) and methyl iodide (5.70 ml, 91 mmol) was dissolved in THF (100 ml). The solution was cooled to −70° C. A solution of NaHMDS in THF (1 M, 91 ml, 91 mmol) was added via syringe over 2 minutes. The reaction solution was stirred for 5 hours at −40 to −70° C. and then was quenched with MeOH (5 ml) and HOAc (3.5 g). The reaction mixture was concentrated. The residue was then partitioned between EtOAc (400 ml) and water (150 ml). The organic phase was separated. The aqueous phase (pH about 7) was extracted with EtOAc (100 ml). The combined organic phases were washed with water (100 ml). The organic solution was then concentrated to give an oil. The residue was purified by silica gel column (220 g silica gel, Hexane/EtOAc 5:1) to afford 11.6 g of 4-benzyl 3-methyl 3-methylmorpholine-3,4-dicarboxylate as an oil (79% yield). 1H NMR (400 MHz, CDCl3) δ=1.58 (s, 3H), 3.23-3.78 (m, 9H), 4.99 (m, 2H), 7.17-7.27 (m, 5H)

1. customwas quenched with MeOH (5 ml) and HOAc (3.5 g)
2. concentrationThe reaction mixture was concentrated
3. customThe residue was then partitioned between EtOAc (400 ml) and water (150 ml)
4. customThe organic phase was separated
5. extractionThe aqueous phase (pH about 7) was extracted with EtOAc (100 ml)
6. washThe combined organic phases were washed with water (100 ml)
7. concentrationThe organic solution was then concentrated
8. customto give an oil
9. customThe residue was purified by silica gel column (220 g silica gel, Hexane/EtOAc 5:1)

ORD record

ord-5045e3985b16416d9be1bf57a25cae53

Source dataset

uspto-grants-2012_04

DOI

10.6084/m9.figshare.5104873.v1

Patent number

US08163755B2