Tetrahydro-4H-pyran-4-one → 4-(6-bromo-2-(4-methoxybenzylamino)quinolin-3-yl)tetrahydro-2H-pyran-4-ol

HRID 1028990Notes

Reaction equation

HRID 1028990 reaction equation
C([Mg]Cl)(C)C.[Br:6][C:7]1[CH:8]=[C:9]2[C:14](=[CH:15][CH:16]=1)[N:13]=[C:12]([NH:17][CH2:18][C:19]1[CH:24]=[CH:23][C:22]([O:25][CH3:26])=[CH:21][CH:20]=1)[C:11](I)=[CH:10]2.[O:28]1[CH2:33][CH2:32][C:31](=[O:34])[CH2:30][CH2:29]1>C1COCC1.[Cl-].[NH4+]>[Br:6][C:7]1[CH:8]=[C:9]2[C:14](=[CH:15][CH:16]=1)[N:13]=[C:12]([NH:17][CH2:18][C:19]1[CH:24]=[CH:23][C:22]([O:25][CH3:26])=[CH:21][CH:20]=1)[C:11]([C:31]1([OH:34])[CH2:32][CH2:33][O:28][CH2:29][CH2:30]1)=[CH:10]2

Participants

6

Reactant 3

HCID 121599Tetrahydro-4H-pyran-4-oneHCID 673456526-bromo-3-iodo-N-(4-methoxybenzyl)quinolin-2-amineHCID 178418918HCID 178418918, compound2×

Product 1

HCID 712533944-(6-bromo-2-(4-methoxybenzylamino)quinolin-3-yl)tetrahydro-2H-pyran-4-ol

Reagents, catalysts & solvents 2

HCID 8028TetrahydrofuranSolvent3×HCID 25517Ammonium ChlorideSolvent

Conditions

Temperature
-20 °C

Procedure

Isopropylmagnesium chloride, 2M THF (1.322 mL, 2.64 mmol) was added to a solution of 6-bromo-3-iodo-N-(4-methoxybenzyl)quinolin-2-amine (1.24 g, 2.64 mmol) in THF (25 mL) cooled to −20° C. After stirring for 5 min, an additional amount of iso-propylmagnesium chloride, 2M THF (1.322 mL, 2.64 mmol) was added and the solution was stirred 10 min at this temperature. Next, dihydro-2H-pyran-4(3H)-one (0.293 mL, 3.17 mmol) was added and the reaction was allowed to come to 0° C. After 20 min, the reaction mixture was diluted with saturated ammonium chloride and extracted with EtOAc. The combined organic extracts were washed with saturated ammonium chloride, water, saturated sodium chloride, and dried over sodium sulfate. The solution was filtered and concentrated in vacuo to give the crude material which was purified by silica gel chromatography by eluting with 1:3 to 1:1 EtOAc in hexane, to provide 4-(6-bromo-2-(4-methoxybenzylamino)quinolin-3-yl)tetrahydro-2H-pyran-4-ol as light-yellow oil.

Workup

  1. stirringthe solution was stirred 10 min at this temperature
  2. customto come to 0° C
  3. waitAfter 20 min
  4. extractionextracted with EtOAc
  5. washThe combined organic extracts were washed with saturated ammonium chloride, water, saturated sodium chloride
  6. dry with materialdried over sodium sulfate
  7. filtrationThe solution was filtered
  8. concentrationconcentrated in vacuo
  9. customto give the crude material which
  10. customwas purified by silica gel chromatography
  11. washby eluting with 1:3 to 1:1 EtOAc in hexane

Sources & evidence

ORD record
ord-fc9fabc90e3941d1a4428ce4b2fdefd7
Source dataset
uspto-grants-2014_05
Patent number
US08735384B2

Reaction notes

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