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0 °C

NMP (1 ml; extra dry) and iron(III) acetylacetonate (35.33 g, 0.0001 mol) were added to a solution of intermediate D8 (498.08 g, 0.001 mol) in THF (10 ml; extra dry) and the mixture was cooled to 0° C. Methylmagnesium bromide (1.67 ml, 0.005 mol) was added slowly and the reaction mixture was stirred for 5 minutes at 0° C. Subsequently, the mixture was quenched with a saturated NH4Cl solution and extracted with CH2Cl2 (3×50 ml). The combined organic layers were washed with brine, dried (MgSO4), filtered and the solvent was evaporated. The residue was redissolved in methanol and NaOH (800 mg, 0.020 mol) was added. The resulting mixture was stirred for 1 hour at room temperature. A saturated NH4Cl solution was added and the mixture was extracted with CH2Cl2 (3×50 ml). The combined organic layers were washed (brine), dried (MgSO4), filtered and the solvent was evaporated in vacuo. The residue was purified by flash column chromatography over silica gel (eluent: (7 N NH3/MeOH)/CH2Cl2 gradiënt from 0/100 to 10/90. The product fractions were collected and the solvent was evaporated in vacuo. The residue was treated with heptane, yielding white crystals. These white crystals were filtered off and dried in vacuo. Yield: 0.632 g of compound E30 (83%; S-enantiomer).

1. customSubsequently, the mixture was quenched with a saturated NH4Cl solution
2. extractionextracted with CH2Cl2 (3×50 ml)
3. washThe combined organic layers were washed with brine
4. dry with materialdried (MgSO4)
5. filtrationfiltered
6. customthe solvent was evaporated
7. dissolutionThe residue was redissolved in methanol
8. stirringThe resulting mixture was stirred for 1 hour at room temperature
9. extractionthe mixture was extracted with CH2Cl2 (3×50 ml)
10. washThe combined organic layers were washed (brine)
11. dry with materialdried (MgSO4)
12. filtrationfiltered
13. customthe solvent was evaporated in vacuo
14. customThe residue was purified by flash column chromatography over silica gel (eluent
15. customThe product fractions were collected
16. customthe solvent was evaporated in vacuo
17. additionThe residue was treated with heptane
18. customyielding white crystals
19. filtrationThese white crystals were filtered off
20. customdried in vacuo