8-Hydroxyquinoline → (S)-tert-butyl 2-(4-(3-(4-fluorophenyl)-1H-1,2,4-triazol-1-yl)phenyl)morpholine-4-carboxylate

HRID 710259Notes

Reaction equation

HRID 710259 reaction equation
[F:1][C:2]1[CH:7]=[CH:6][C:5]([C:8]2[N:12]=[CH:11][NH:10][N:9]=2)=[CH:4][CH:3]=1.Br[C:14]1[CH:19]=[CH:18][C:17]([C@@H:20]2[O:25][CH2:24][CH2:23][N:22]([C:26]([O:28][C:29]([CH3:32])([CH3:31])[CH3:30])=[O:27])[CH2:21]2)=[CH:16][CH:15]=1.C(=O)([O-])[O-].[Cs+].[Cs+].OC1C=CC=C2C=1N=CC=C2>CN(C)C=O.O.[Cu]I.C(OCC)(=O)C>[F:1][C:2]1[CH:3]=[CH:4][C:5]([C:8]2[N:12]=[CH:11][N:10]([C:14]3[CH:15]=[CH:16][C:17]([C@@H:20]4[O:25][CH2:24][CH2:23][N:22]([C:26]([O:28][C:29]([CH3:32])([CH3:31])[CH3:30])=[O:27])[CH2:21]4)=[CH:18][CH:19]=3)[N:9]=2)=[CH:6][CH:7]=1

Participants

9

Reactant 4

HCID 19238-HydroxyquinolineHCID 10796Cesium carbonateHCID 58097875tert-butyl (2S)-2-(4-bromophenyl)morpholine-4-carboxylateHCID 178505560HCID 178505560, compound

Product 1

HCID 89689407(S)-tert-butyl 2-(4-(3-(4-fluorophenyl)-1H-1,2,4-triazol-1-yl)phenyl)morpholine-4-carboxylate

Reagents, catalysts & solvents 4

HCID 24350Copper(1+) iodide; Copper(I) iodide; Cuprous iodide; Cuprous iodide (CuI)CatalystHCID 962WaterSolvent2×HCID 6228DimethylformamideSolventHCID 8857Ethyl AcetateSolvent

Conditions

Temperature
150 °C

Procedure

3-(4-Fluorophenyl)-1H-1,2,4-triazole (CAS [95728-10-2], 200 mg, 0.9 mmol) was dissolved in a mixture of dimethylformamide and water (5.5 ml; v/v=10:1) and (S)-tert-butyl 2-(4-bromophenyl)morpholine-4-carboxylate (368 mg, 1.08 mmol), cesium carbonate (1.46 g, 4.48 mmol), copper(I)-iodide (5.1 mg, 0.027 mmol) and 8-hydroxyquinoline (4 mg, 0.027 mmol) were added successively. The glass was closed and the reaction mixture was allowed to stir at 150° C. for 48 h. According to TLC, the reaction was finished. After cooling, water and ethyl acetate were added. The organic layer was dried over MgSO4 and evaporated. The crude material was purified by flash chromatography (silica gel, gradient heptane/ethyl acetate), off-white solid (205 mg, 54%), MS (ISP): 425.2 ([M+H]+).

Workup

  1. additionwere added successively
  2. customThe glass was closed
  3. temperatureAfter cooling
  4. dry with materialThe organic layer was dried over MgSO4
  5. customevaporated
  6. customThe crude material was purified by flash chromatography (silica gel, gradient heptane/ethyl acetate), off-white solid (205 mg, 54%), MS (ISP)

Sources & evidence

ORD record
ord-e44baf33de2b491795532accbeb81cd4
Source dataset
uspto-grants-2015_11
Patent number
US09181230B2

Reaction notes

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