2-Bromo-4-fluoroanisole → Tert-butyl 4-(5-fluoro-2-methoxybenzyl)-4-hydroxypiperidine-1-carboxylate
Reaction equation
C([Mg]Cl)(C)C.Br[C:7]1[CH:12]=[C:11]([F:13])[CH:10]=[CH:9][C:8]=1[O:14][CH3:15].[O:16]1[C:18]2([CH2:23][CH2:22][N:21]([C:24]([O:26][C:27]([CH3:30])([CH3:29])[CH3:28])=[O:25])[CH2:20][CH2:19]2)[CH2:17]1>O1CCCC1.O>[C:27]([O:26][C:24]([N:21]1[CH2:22][CH2:23][C:18]([CH2:17][C:7]2[CH:12]=[C:11]([F:13])[CH:10]=[CH:9][C:8]=2[O:14][CH3:15])([OH:16])[CH2:19][CH2:20]1)=[O:25])([CH3:30])([CH3:28])[CH3:29]Participants
Reactant 3
Product 1
Reagents, catalysts & solvents 2
Conditions
- Temperature
- 20 °C
Procedure
A solution of iso-propylmagnesium chloride in tetrahydrofuran (2M, 130 mL) was added dropwise over 30 minutes to a stirred solution of 2-bromo-4-fluoroanisole (34.2 mL) in anhydrous tetrahydrofuran (400 mL) at 30° C. under nitrogen. After a further 16 hours at 30° C., copper (I) bromide dimethyl sulphide complex (0.4 g) was added followed by solution of tert-butyl 1-oxa-6-azaspiro[2.5]octane-6-carboxylate (56.2 g) in anhydrous tetrahydrofuran (110 mL). After a further 3 hours at 30° C., the solution was cooled to 20° C., diluted with water (600 mL) and extracted with tert.-butyl methyl ether (600 mL) then ethyl acetate (600 mL). Combined organic extracts were dried over anhydrous magnesium sulphate, filtered and evaporated under reduced pressure to give crude sub-title compound (86 g) as a solid.
Workup
- additioncopper (I) bromide dimethyl sulphide complex (0.4 g) was added
- waitAfter a further 3 hours at 30° C.
- extractionextracted with tert.-butyl methyl ether (600 mL)
- dry with materialCombined organic extracts were dried over anhydrous magnesium sulphate
- filtrationfiltered
- customevaporated under reduced pressure
Sources & evidence
- ORD record
- ord-b148790c5e4e4952ad593e3dd2e77d7e
- Source dataset
- uspto-grants-2009_04
- Patent number
- US07524856B2
Reaction notes
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