Tetrahydrofuran → (S)-4-hydroxy-6-[2-(4-hydroxy-phenyl)-ethyl]-6-isopropyl-5,6-dihydro-pyran-2-one

Reaktionsgleichung

[OH:1][C@:2]([CH2:10][CH2:11][C:12]1[CH:17]=[CH:16][C:15]([OH:18])=[CH:14][CH:13]=1)([CH:7]([CH3:9])[CH3:8])[CH2:3][C:4]([OH:6])=O.C1N=CN(C(N2C=NC=C2)=O)C=1.C1C[O:34][CH2:33][CH2:32]1>>[OH:6][C:4]1[CH2:3][C@@:2]([CH2:10][CH2:11][C:12]2[CH:17]=[CH:16][C:15]([OH:18])=[CH:14][CH:13]=2)([CH:7]([CH3:9])[CH3:8])[O:1][C:33](=[O:34])[CH:32]=1

Komponenten

Edukt 3

HCID 8028Tetrahydrofuran

HCID 682631,1'-Carbonyldiimidazole

HCID 53816519(S)-3-hydroxy-3-[2-(4-hydroxy-phenyl)-ethyl]4-methyl-pentanoic acid

Produkt 1

HCID 54682331(S)-4-hydroxy-6-[2-(4-hydroxy-phenyl)-ethyl]-6-isopropyl-5,6-dihydro-pyran-2-one

Versuchsvorschrift

The title compound was prepared using (S)-3-hydroxy-3-[2-(4-hydroxy-phenyl)-ethyl]4-methyl-pentanoic acid (0.45 g, 1.78 mmol) from Example UUUU, THF (10 mL), and CDI (0.58 g, 3.58 mmol). The reaction was stirred 15 overnight at room temperature then added to bis[3-ethoxy-3-oxopropanoato(1-)-O,O']-magnesate (1.5 g, 5.2 mmol) from Example VVVV and the reaction stirred for 3 days at room temperature. The reaction was concentrated and the residue partitioned between ethyl acetate and 1N HCl. The organic layer was washed with aqueous NaHCO3 and brine, dried (MgSO4) and concentrated. 20 The crude product was cyclized as described in General Method 7 using 10 mL of THF and 150 mL of 0.1N NaOH. Purification by silica gel chromatography, eluting with CH2Cl2 :MeOH (98:2) gave the title compound. 1H-NMR (DMSO-d6) δ 0.83 (d, 3 H), 0.86 (d, 3 H), 1.78 (m, 2 H), 2.06 (m, 1 H), 2.25 (d of ABX q, 1 H), 2.39 (m, 2 H), 2.53 (d of ABX q, 1 H), 4.89 (s, 1 H), 6.6 (d, 2 H), 6.89 (d, 2 H), 9.1 (br s, 1 H).