4-Methylmorpholine → HCID 13685965, compound

4.98 g (20 mmol) N-carbobenzoxy-D-proline, 2.73 g (20 mmol) isobutyl chloroformate, 2.02 g (20 mmol) N-methylmorpholine, and 2.73 g (26.5 mmol) DL-valinol were contacted and reacted in THF substantially according to the mixed anhydride procedure described in Example 1. The resulting crude product, 7.23 g, was dissolved in 25 mL hot ethyl acetate, and 25 mL n-hexane were added. The resulting solution was filtered, seeded with a crystal of N-carbobenzoxy-D-prolyl-D-valinol, and allowed to stand for one hour. The resulting crystalline product of the undesired DL isomer was separated, and the solvent was evaporated from the filtrate. The residue was dissolved in 5 mL hot ethanol, to which 50 mL cold n-hexane were added. After filtration, 750 ml additional n-hexane were added to the filtrate, the resulting solution seeded, and crystalline product D-D was separated. This ethanol/n-hexane recrystallization step was repeated with the D-D crude product to provide 330 mg (0.99 mmol, 5%) N-carbobenzoxy-D-prolyl-D-valinol (D-D isomer), m.p. 113°-114°, α 25D+67.6° (C=1.0 g/100 mL in acetone).

1. filtrationThe resulting solution was filtered
2. customThe resulting crystalline product of the undesired DL isomer was separated
3. customthe solvent was evaporated from the filtrate
4. dissolutionThe residue was dissolved in 5 mL hot ethanol, to which 50 mL cold n-hexane
5. additionwere added
6. filtrationAfter filtration, 750 ml additional n-hexane
7. additionwere added to the filtrate
8. customcrystalline product D-D was separated
9. customThis ethanol/n-hexane recrystallization step

ORD record

ord-c5c92e06388c409cb85ce7f26389a5d4

Source dataset

uspto-grants-1985_04

DOI

10.6084/m9.figshare.5104873.v1

Patent number

US04511390