Potassium Carbonate → 3-(4-Amino-2-fluorophenyl)-3-hydroxy-1-(1,1-diphenylmethyl)azetidine

Sec. butyllithium (22.5 mL of a 1.3M solution in cyclohexane, 29.5 mmol) was added dropwise to a stirred solution of 1-(3-fluorophenyl)-2,2,5,5-tetramethyl-1-aza-2,5-disilacyclopentane (Example 20, Step 1) (6.0 g, 23.7 mmol) at -78° C. under nitrogen in dry THF (75 mL). After 2 hr a solution of 1-(1,1-diphenylmethyl)azetidin-3-one (5.6 g, 23.6 mmol) in dry THF (60 mL) was added dropwise and stirring continued at -78° for 2 hr, when the cooling bath was removed. After reaching room temperature, a solution of saturated ammonium chloride (75 mL) was added followed by water (200 mL). The mixture was extracted with ether (500 mL), washed with brine (100 mL), dried over magnesium sulfate, filtered and evaporated. The residue was dissolved in methanol (150 mL) and anhydrous potassium carbonate (6.0 g, 43.5 mmol) added and then stirred overnight. The suspension was filtered and the filtrate evaporated. The residue was partitioned between ether (500 mL) and water (200 mL). The water was extracted with additional ether (200 mL) and the combined ether extracts washed with brine (100 mL), dried over magnesium sulfate, filtered and evaporated to afford an orange foam. Chromatography over silica gel (150 g, 40-60 μm) eluting with 25-50% ethyl acetate-hexane gave the title compound as a pale yellow foam. 1H NMR δ (CDCl3): 2.62, 3.53, 3.78, 4.41, 6.36, 6.41, 7.03, 7.14-7.30, 7.39-7.47.

1. customwhen the cooling bath was removed
2. customAfter reaching room temperature
3. additiona solution of saturated ammonium chloride (75 mL) was added
4. extractionThe mixture was extracted with ether (500 mL)
5. washwashed with brine (100 mL)
6. dry with materialdried over magnesium sulfate
7. filtrationfiltered
8. customevaporated
9. dissolutionThe residue was dissolved in methanol (150 mL)
10. stirringstirred overnight
11. filtrationThe suspension was filtered
12. customthe filtrate evaporated
13. customThe residue was partitioned between ether (500 mL) and water (200 mL)
14. extractionThe water was extracted with additional ether (200 mL)
15. washthe combined ether extracts washed with brine (100 mL)
16. dry with materialdried over magnesium sulfate
17. filtrationfiltered
18. customevaporated
19. customto afford an orange foam
20. washChromatography over silica gel (150 g, 40-60 μm) eluting with 25-50% ethyl acetate-hexane

ORDレコード

ord-51fc69dde5dd464780f767eb40186293

出典データセット

uspto-grants-2000_04

DOI

10.6084/m9.figshare.5104873.v1

特許番号

US06051716