Hydrochloric Acid → 2'-Chloro-4',4'-difluoro-4',5'-dihydrospiro[piperidine-4,7'-[7H]thieno[2,3-c]pyran]

Temperature

45 °C

37% Hydrochloric acid (74.12 mL, 789.78 mmol) is added to a solution of tert-butyl 2′-chloro-4′,4′-difluoro-4′,5′-dihydrospiro[piperidine-4,7′-thieno[2,3-c]pyran]-1-carboxylate (60 g, 157.96 mmol) in isopropyl alcohol (420 mL) at 45° C. The resulting solution is stirred at 45° C. for 15 h. Then, the mixture is concentrated to 1/4 volume to afford a white suspension. Water (100 mL) is added and the suspension is basified with 6N aqueous solution of sodium hydroxide to obtain a two-layer mixture that is extracted with methyl t-butyl ether (3×100 mL). Combined organics are washed with brine (50 mL), dried over sodium sulfate and concentrated to afford a light brown solid which is dried under vacuum till constant weigh to yield 97% of the title compound. MS (m/z): 280 (M+1).

1. concentrationThen, the mixture is concentrated to 1/4 volume
2. customto afford a white suspension
3. customto obtain a two-layer mixture that
4. extractionis extracted with methyl t-butyl ether (3×100 mL)
5. washCombined organics are washed with brine (50 mL)
6. dry with materialdried over sodium sulfate
7. concentrationconcentrated
8. customto afford a light brown solid which
9. customis dried under vacuum

ORD record

ord-b71835d17cf8484bafa16e08bdfb6a55

Source dataset

uspto-grants-2012_07

DOI

10.6084/m9.figshare.5104873.v1

Patent number

US08232289B2