Sodium hydride → HCID 118007233, compound

Temperature

0 °C

To stirred suspension of sodium hydride (203.1 mg, 5.1 mmol as a 60% oil dispersion) in THF (18 mL) cooled to 0° C. was added dropwise (S)—N—((R)-3-(benzyloxy)-2-hydroxypropyl)-2-chlorobutanamide (362.8 mg, 1.270 mmol) in THF (3.8 mL) over a 5-min period after which the reaction was stirred at 0° C. for 30 min followed by stirring at rt for 5 h. The completed reaction was quenched with the slow addition of IPA (1 mL) followed by adding Dowex 50, H+ form, until a neutral to acidic pH was observed. The final suspension was filtered and the solid was rinsed two times with EtOAc. The combined filtrated were concentrated and the resultant crude product was purified over silica gel (Biotage, eluting with 1:1 EtOAc:heptane). The desired fractions were combined, concentrated and dried in vacuo to provide (2R,6R)-6-((benzyloxy)methyl)-2-ethylmorpholin-3-one (314 mg, 1.260 mmol, 99.2% yield).

1. stirringwas stirred at 0° C. for 30 min
2. stirringby stirring at rt for 5 h
3. customThe completed reaction
4. customwas quenched with the slow addition of IPA (1 mL)
5. additionby adding Dowex 50, H+ form
6. filtrationThe final suspension was filtered
7. washthe solid was rinsed two times with EtOAc
8. filtrationThe combined filtrated
9. concentrationwere concentrated
10. customthe resultant crude product was purified over silica gel (Biotage, eluting with 1:1 EtOAc:heptane)
11. concentrationconcentrated
12. customdried in vacuo

ORD record

ord-abc41179e3904418b587de5b226b59ae

Source dataset

uspto-grants-2016_08

DOI

10.6084/m9.figshare.5104873.v1

Patent number

US09428495B2