N1CCCC1.[F:6][C:7]1[C:8]([OH:16])=[C:9]([C:13](=[O:15])[CH3:14])[CH:10]=[CH:11][CH:12]=1.[O:17]1[CH2:22][CH2:21][C:20](=O)[CH2:19][CH2:18]1.Cl>C1(C)C=CC=CC=1>[F:6][C:7]1[CH:12]=[CH:11][CH:10]=[C:9]2[C:8]=1[O:16][C:20]1([CH2:21][CH2:22][O:17][CH2:18][CH2:19]1)[CH2:14][C:13]2=[O:15]Pyrrolidine (4.8 ml, 58 mmol) was added to a stirred solution of 1-(3-fluoro-2-hydroxyphenyl)ethanone (28) (5.9 g, 39 mmol) and tetrahydro-4h-pyran-4-one (4.6 ml, 50 mmol) in toluene (40 mL) at rt. After the exotherm subsided, the reaction mixture was stirred at rt for 1 h. then subjected to Dean-Stark reflux conditions for 6 h. The reaction mixture was cooled, poured into ice and 2 N HCl aqueous solution, and extracted with EtOAc (2×). The combined organics were washed with 2 N HCl aqueous solution (1×), 2 N NaOH aqueous solution (2×), brine (1×), and dried over Na2SO4. Concentration in vacuo gave 8-fluoro-2′,3′,5′,6′-tetrahydrospiro[chromene-2,4′-pyran]-4(3H)-one (29) (4.4 g, 48% yield) which was taken onto the next step without further purification. 1H NMR (400 MHz, DMSO-d6) δ ppm 7.51-7.60 (2H, m), 7.00-7.07 (1H, m), 3.60-3.73 (4H, m), 2.93 (2H, s), 1.71-1.92 (4H, m).
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