1-Bromo-4-fluorobenzene → HCID 118105579, compound
Reaction equation
[CH2:1]([N:8]1[CH:13]2[CH2:14][CH2:15][CH:9]1[CH2:10][NH:11][CH2:12]2)[C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][CH:3]=1.C1(P(C2C=CC=CC=2)C2C=CC3C(=CC=CC=3)C=2C2C3C(=CC=CC=3)C=CC=2P(C2C=CC=CC=2)C2C=CC=CC=2)C=CC=CC=1.CC(C)([O-])C.[Na+].Br[C:69]1[CH:74]=[CH:73][C:72]([F:75])=[CH:71][CH:70]=1>O1CCOCC1>[CH2:1]([N:8]1[C@H:13]2[CH2:14][CH2:15][C@@H:9]1[CH2:10][N:11]([C:69]1[CH:74]=[CH:73][C:72]([F:75])=[CH:71][CH:70]=1)[CH2:12]2)[C:2]1[CH:3]=[CH:4][CH:5]=[CH:6][CH:7]=1Participants
Conditions
- Temperature
- 100 °C
Procedure
To a stirred solution of 8-benzyl-3,8-diazabicyclo[3.2.1]octane (2.5 g, 12.36 mmol) in 1,4-dioxane (15 ml) in sealed tube at 25° C. was added 2,2′-Bis(diphenylphosphino)-1,1′-binaphthyl (0.770 g, 1.23 mmol), sodium tert-butoxide (2.37 g, 24.72 mmol), 1-bromo-4-fluorobenzene (1.63 ml, 14.83 mmol) and tris(dibenzyllideneacetone)dipalladium (0) [Pd2(dba)3] (0.566 g, 0.618 mmol). The resulting reaction mixture was purged with nitrogen for 10 min and stirred at 100° C. for 15 h. The reaction mixture was then cooled to 25° C., filtered through a celite bed, and the celite bed was washed with ethyl acetate (2×20 ml). The combined filtrate was concentrated under reduced pressure to get crude compound. The resulting crude compound was purified by using flash column chromatography over silica gel (100-200 mesh) using 10% ethylacetate in hexane to obtain title compound (2.4 g 66%).
Workup
- customThe resulting reaction mixture
- customwas purged with nitrogen for 10 min
- temperatureThe reaction mixture was then cooled to 25° C.
- filtrationfiltered through a celite bed
- washthe celite bed was washed with ethyl acetate (2×20 ml)
- concentrationThe combined filtrate was concentrated under reduced pressure
- customto get crude compound
- customThe resulting crude compound was purified
Sources & evidence
- ORD record
- ord-862b54ab56d64a5e8306677abf6d7d93
- Source dataset
- uspto-grants-2016_06
- Patent number
- US09359367B2
Reaction notes
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