Water → HCID 89782052, compound

HRID 1055916Notes

Reaction equation

HRID 1055916 reaction equation
[N:1]1([C:7]([C:9]2[CH:18]=[CH:17][C:16]3[C:11](=[C:12]([C:19](=[O:21])[CH3:20])[CH:13]=[CH:14][CH:15]=3)[N:10]=2)=[O:8])[CH2:6][CH2:5][O:4][CH2:3][CH2:2]1.[Si](OS(C(F)(F)F)(=O)=O)(C(C)(C)C)(C)C.O.C1C(=O)N([Br:45])C(=O)C1>C(Cl)Cl.C1COCC1>[Br:45][CH2:20][C:19]([C:12]1[CH:13]=[CH:14][CH:15]=[C:16]2[C:11]=1[N:10]=[C:9]([C:7]([N:1]1[CH2:6][CH2:5][O:4][CH2:3][CH2:2]1)=[O:8])[CH:18]=[CH:17]2)=[O:21]

Participants

7

Reactant 4

HCID 962WaterHCID 67184N-bromobutanimideHCID 123564tert-Butyldimethylsilyl trifluoromethanesulphonateHCID 89782323HCID 89782323, compound

Product 1

HCID 89782052HCID 89782052, compound

Reagents, catalysts & solvents 2

HCID 6344DichloromethaneSolventHCID 8028TetrahydrofuranSolvent

Conditions

Temperature
0 °C

Procedure

To a solution of 1-(2-(morpholine-4-carbonyl)quinolin-8-yl)ethanone (0.438 g, 1.54 mmol) in DCM (5 mL) at 0° C. was added TEA (0.28 ml, 2.00 mmol) followed by TBSOTf (0.39 mL, 1.70 mmol). The resulting mixture was stirred at 0° C. for 50 min. The mixture was then partitioned between saturated NaHCO3 and DCM. The organic layer was separated, and the aq. layer was extracted with DCM (3×). The combined organic layers were then dried over anhydrous MgSO4, filtered, and concentrated in vacuo to give a brown oil. The resulting oil was taken up in THF (8 mL) and treated with water (0.44 mL, 24.7 mmol) and NBS (288 mg, 1.62 mmol). The resulting solution was stirred at RT for 20 min. The reaction mixture was then partitioned between water and Et2O, and the organic layer was separated and sequentially washed with saturated NaHCO3, water, and brine, then dried over MgSO4, filtered, and concentrated in vacuo to give a 2-bromo-1-(2-(morpholine-4-carbonyl)quinolin-8-yl)ethanone as a greenish-brown solid. This material was used in the subsequent step without purification, assuming the theoretical yield: 1H NMR (400 MHz, DMSO-d6) δ ppm 8.66 (d, J=8.6 Hz, 1H), 8.29 (dd, J=8.1, 1.3 Hz, 1H), 8.11 (dd, J=7.2, 1.4 Hz, 1H), 7.77-7.85 (m, 2H), 3.72 (s, 4H), 3.61-3.62 (m, 2H), 3.57-3.59 (m, 2H), 3.51-3.57 (m, 2H). m/z (ESI, +ve ion) 363.0/365.0 (M+H)+.

Workup

  1. customThe mixture was then partitioned between saturated NaHCO3 and DCM
  2. customThe organic layer was separated
  3. extractionthe aq. layer was extracted with DCM (3×)
  4. dry with materialThe combined organic layers were then dried over anhydrous MgSO4
  5. filtrationfiltered
  6. concentrationconcentrated in vacuo
  7. customto give a brown oil
  8. stirringThe resulting solution was stirred at RT for 20 min
  9. customThe reaction mixture was then partitioned between water and Et2O
  10. customthe organic layer was separated
  11. washsequentially washed with saturated NaHCO3, water, and brine
  12. dry with materialdried over MgSO4
  13. filtrationfiltered
  14. concentrationconcentrated in vacuo

Sources & evidence

ORD record
ord-a20e3a9115254f54a8a751e9b604a8fb
Source dataset
uspto-grants-2016_07
Patent number
US09394297B2

Reaction notes

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