反应详情

To a degassed solution of 5-tert-butoxycarbonylamino-3-(3,5-difluoro-4-nitro-benzyl)-4-oxo-tetrahydro-thiopyran-3-carboxylic acid allyl ester (30.4 g, 62.4 mmol) in THF (300 mL) was added under argon 5,5-dimethyl-cyclohexane-1,3-dione (11.6 g, 81.2 mmol) and Pd(PPh3)4 (0.76 g, 0.62 mmol) and the reaction mixture was stirred for 3 h at 25° C. The reaction mixture was poured into aq. NaH2PO4 solution, concentrated and extracted with EtOAc. Combined organic extracts were washed with brine, dried over MgSO4, filtered and evaporated. The crystallized product containing the (3R*,5S*)-diastereoisomer was filtered off and dried. The mother liquor containing a larger amount of the (3S*,5S*)-diastereoisomer was dissolved in THF and equilibrated with a catalytic amount of DBU to the (3R*,5S*)-diastereoisomer for 16 h at 25° C. After removal of the THF the (3R*,5S*)-diastereoisomer was crystallized from Et2O-hexane to provide more of the title compound as white crystals: TLC (hexane-EtOAc 3:1) Rf=0.23; HPLC RtA=2.23 min; ESIMS [M+NH4]+=420; 1H NMR (400 MHz, CDCl3): δ 6.96 (d, 2H), 5.65 (d, 1H), 4.55 (m, 1H), 3.40 (m, 1H), 3.25 (dd, 1H), 3.14 (m, 1H), 2.86 (m, 1H), 2.6-2.75 (m, 3H), 1.44 (s, 9H).

1. concentrationconcentrated
2. extractionextracted with EtOAc
3. washCombined organic extracts were washed with brine
4. dry with materialdried over MgSO4
5. filtrationfiltered
6. customevaporated
7. additionThe crystallized product containing the (3R*,5S*)-diastereoisomer
8. filtrationwas filtered off
9. customdried
10. additionThe mother liquor containing a larger amount of the (3S*,5S*)-diastereoisomer
11. dissolutionwas dissolved in THF
12. customAfter removal of the THF the (3R*,5S*)-diastereoisomer
13. customwas crystallized from Et2O-hexane