反应详情

Dissolve [4-(2-azepan-1-yl-ethoxy)-phenyl]-[2-(2,6-difluoro-phenyl)-6-hydroxy-naphthalen-1-yl]-methanone (1.3 g, 2.6 mmol) in 125 mL dioxane and add 20 mL (20 mmol) of a 1.0 M solution of lithium triethylborohydride in THF. Stir at room temperature for one hour, then heat at 100° C. for three hours. Pour the reaction into a two phase system consisting of saturated sodium bicarbonate and an organic phase of a 3/1 mixture of chloroform/isopropanol. Extract in a reparatory funnel, separate the organic layer and dry over 3 Å molecular sieves. Evaporate to give 1.5 g of slightly impure product. Purify on a silica column eluting with 0-10% methanol/methylene chloride gradient to give 850 mg (68%) of racemic product: 1H-NMR (CDCl3, 400 MHz) δ8.18 (d, J=8.4 Hz, 1H); 7.73 (d, J=8.8 Hz, 1H); 7.52 (d, J=9.2 Hz, 1H); 7.21 (d, J=2.4 Hz, 1H); 7.08-6.99 (m, 5H); 6.88 (s, 1H); 6.72-6.61 (m, 4H); 4.24-4.23 (m, 2H); 3.26-3.26 (m, 6H); 1.87-1.87 (m, 4H); 1.66-1.66 (m, 4H). The racemic mixture is purified using chiral chromatography (conditions F). The two isomers eluted with retention times of 7.9 and 9.0 minutes.

1. temperatureheat at 100° C. for three hours
2. additionPour
3. customthe reaction into a two phase system
4. extractionExtract in a reparatory funnel
5. customseparate the organic layer
6. customdry over 3 Å molecular sieves
7. customEvaporate
8. customto give 1.5 g of slightly impure product
9. customPurify on a silica column
10. washeluting with 0-10% methanol/methylene chloride gradient