Morpholine → 4-(5-Bromopyridin-3-yl)morpholine
Reaction equation
Br[C:2]1[CH:3]=[N:4][CH:5]=[C:6]([Br:8])[CH:7]=1.[NH:9]1[CH2:14][CH2:13][O:12][CH2:11][CH2:10]1.C(Cl)(Cl)Cl.O>O1CCOCC1.C1C=CC(/C=C/C(/C=C/C2C=CC=CC=2)=O)=CC=1.C1C=CC(/C=C/C(/C=C/C2C=CC=CC=2)=O)=CC=1.C1C=CC(/C=C/C(/C=C/C2C=CC=CC=2)=O)=CC=1.[Pd].[Pd].CC1(C)C2C(=C(P(C3C=CC=CC=3)C3C=CC=CC=3)C=CC=2)OC2C(P(C3C=CC=CC=3)C3C=CC=CC=3)=CC=CC1=2>[Br:8][C:6]1[CH:7]=[C:2]([N:9]2[CH2:14][CH2:13][O:12][CH2:11][CH2:10]2)[CH:3]=[N:4][CH:5]=1Participants
7
Reactant 3
Product 1
Reagents, catalysts & solvents 3
Procedure
To a solution of 3,5-dibromopyridine (XL) (1.68 g, 7.1 mmol) in dioxane (14 mL) was added morpholine (682 mg, 7.8 mmol), CsCO3 (3.24 g, 9.93 mmol) and xantphos (123 mg, 0.21 mmol). The solution was degassed before adding Pd2(dba)3 (195 mg, 0.21 mmol). The reaction was microwaved at 90° C. for 4 h. The reaction was poured into a mixture of CHCl3/H2O; the aqueous layer was separated, washed with water, then brine and concentrated under vacuum. The crude product was purified on a silica gel column (100% hexane→1:3 EtOAc:hexane) to give 4-(5-bromopyridin-3-yl)morpholine (XLI) as a yellow solid (1.12 g, 4.6 mmol, 65% yield). ESIMS found C9H11BrN2O m/z 244 (M+H).
Workup
- customThe solution was degassed
- customThe reaction was microwaved at 90° C. for 4 h
- customthe aqueous layer was separated
- washwashed with water
- concentrationbrine and concentrated under vacuum
- customThe crude product was purified on a silica gel column (100% hexane→1:3 EtOAc:hexane)
Sources & evidence
- ORD record
- ord-26cc3755a0244595a21190400d73ab2a
- Source dataset
- uspto-grants-2015_03
- Patent number
- US08987298B2
Reaction notes
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