Morpholine → 4-(5-Bromo-1,3-thiazol-2-yl)morpholine

HRID 1926310Notes

Reaction equation

HRID 1926310 reaction equation
Br[C:2]1[S:3][C:4]([Br:7])=[CH:5][N:6]=1.[NH:8]1[CH2:13][CH2:12][O:11][CH2:10][CH2:9]1>CCN(C(C)C)C(C)C>[Br:7][C:4]1[S:3][C:2]([N:8]2[CH2:13][CH2:12][O:11][CH2:10][CH2:9]2)=[N:6][CH:5]=1

Participants

4

Reactant 2

HCID 8083MorpholineHCID 3123942,5-Dibromothiazole

Product 1

HCID 457875514-(5-Bromo-1,3-thiazol-2-yl)morpholine

Reagents, catalysts & solvents 1

HCID 81531DiisopropylethylamineSolvent

Conditions

Temperature
110 °C

Procedure

A solution of 2,5-dibromothiazole (0.500 g, 2.06 mmol) in DIPEA (1.50 mL) was charged with morpholine (0.179 mL, 2.06 mmol) and heated to 110° C. for 2 h. The reaction mixture was allowed to cool then partitioned between EtOAc and H2O, and the layers were separated. The aqueous layer was re-extracted with EtOAc (3×), and the combined organic extracts were washed with brine (2×), dried over Na2SO4, filtered and concentrated in vacuo. The crude material was purified by chromatography on silica gel [eluting with 5% EtOAc in CHCl3] resulting in the title compound as an off-white solid. 1H NMR (400 MHz, CDCl3): δ=3.35-3.47 (m, 4H), 3.74-3.86 (m, 4H), 7.09 (s, 1H). MS (ES+): m/z=249.06/251.03 (51/49) [MH+]. HPLC: tR=2.98 min (ZQ2, polar—5 min).

Workup

  1. temperatureto cool
  2. customthen partitioned between EtOAc and H2O
  3. customthe layers were separated
  4. extractionThe aqueous layer was re-extracted with EtOAc (3×)
  5. washthe combined organic extracts were washed with brine (2×)
  6. dry with materialdried over Na2SO4
  7. filtrationfiltered
  8. concentrationconcentrated in vacuo
  9. customThe crude material was purified by chromatography on silica gel [eluting with 5% EtOAc in CHCl3]

Sources & evidence

ORD record
ord-be12f09e156c4fbcb16da9d6a3bbdd02
Source dataset
uspto-grants-2012_05
Patent number
US08178668B2

Reaction notes

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