Morpholine → 4-(5-Bromopyridin-3-yl)morpholine

HRID 1187337Notes

Reaction equation

HRID 1187337 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]=1

Participants

7

Reactant 3

HCID 8083MorpholineHCID 693693,5-DibromopyridineHCID 22418719Chloroform water

Product 1

HCID 467396144-(5-Bromopyridin-3-yl)morpholineYield 65%

Reagents, catalysts & solvents 3

HCID 6360441,1'-(9,9-Dimethyl-9H-xanthene-4,5-diyl)bis(1,1-diphenylphosphine)CatalystHCID 9811564Bis(dibenzylideneacetone)palladiumCatalystHCID 312751,4-DioxaneSolvent

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

  1. customThe solution was degassed
  2. customThe reaction was microwaved at 90° C. for 4 h
  3. customthe aqueous layer was separated
  4. washwashed with water
  5. concentrationbrine and concentrated under vacuum
  6. customThe crude product was purified on a silica gel column (100% hexane→1:3 EtOAc:hexane)

Sources & evidence

ORD record
ord-5717cb93cea64d8bafa92f7ab42b2e9b
Source dataset
uspto-grants-2014_03
Patent number
US08673936B2

Reaction notes

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