1-[2-(4-Iodophenoxy)ethyl]piperidine → 1-{2-[4-(5,11-Bis{[tert-butyl(dimethyl)silyl]oxy}-1,8-dihydro-2H-[1]benzopyrano[4,3-d][1]benzoxepin-8-yl)phenoxy]ethyl}piperidine

Temperature

-78 °C

1-[2-(4-Iodo-phenoxy)-ethyl]-piperidine (150 mg, 0.453 mmol) was dissolved in THF and cooled to −78° C. To the reaction mixture was then added n-butyl lithium (2M solution in pentane, 226 μl), slowly over 5 min. The reaction mixture was stirred for 1 h at −78° C. In a separate flask, 2,8-bis-(tert-butyl-dimethyl-silyloxy)-11,12-dihydro-5H-6,13-dioxa-benzo[3,4]cyclohepta[1,2-a]naphthalen-5-ol (28 mg, 0.053 mmol)) was dissolved in THF (1 mL) and added to the reaction mixture containing the 1-[2-(4-Iodo-phenoxy)-ethyl]-piperidine and n-butyl lithium, slowly over 5 min. The reaction mixture was stirred for additional 1 hr. The reaction mixture was quenched by MeOH (0.5 mL), treated with a saturated solution of ammonium chloride (30 mL) and then diluted with diethyl ether (25 mL). The organic layer was separated and washed with brine (15 mL). The organic layer was dried over anhydrous Na2SO4, filtered and the solvent evaporated to yield a crude oil. The crude oil was diluted with toluene (30 mL) and 1 N HCl (6.0 mL) and then stirred for 30 min at room temperature. The reaction mixture was diluted with EtOAc (20 mL) and the organic layer was washed twice with water (20 ml) and with a saturated solution of NaHCO3 (10 ml). The organic layer was separated, dried over anhydrous Na2SO4, filtered and evaporated to yield 1-(2-{4-[2,8-Bis-(tert-butyl-dimethyl-silyloxy)-11,12-dihydro-5H-6,13-dioxa-benzo[3,4]cyclohepta[1,2-a]naphthalen-5-yl]-phenoxy}-ethyl)piperidine as an oil.

1. additionadded to the reaction mixture
2. waitslowly over 5 min
3. stirringThe reaction mixture was stirred for additional 1 hr
4. customThe reaction mixture was quenched by MeOH (0.5 mL)
5. additiontreated with a saturated solution of ammonium chloride (30 mL)
6. additiondiluted with diethyl ether (25 mL)
7. customThe organic layer was separated
8. washwashed with brine (15 mL)
9. dry with materialThe organic layer was dried over anhydrous Na2SO4
10. filtrationfiltered
11. customthe solvent evaporated
12. customto yield a crude oil
13. stirringstirred for 30 min at room temperature
14. washthe organic layer was washed twice with water (20 ml) and with a saturated solution of NaHCO3 (10 ml)
15. customThe organic layer was separated
16. dry with materialdried over anhydrous Na2SO4
17. filtrationfiltered
18. customevaporated

ORD record

ord-d13142f7fd744ce1a8b5cae74b8e0298

Source dataset

uspto-grants-2008_02

DOI

10.6084/m9.figshare.5104873.v1

Patent number

US07329654B2