3,4-dihydro-2H-pyran → 3-bromo-1-(oxan-2-yl)-1H-indazole

HRID 1671278Notes

Reaction equation

HRID 1671278 reaction equation
[Br:1][C:2]1[C:10]2[C:5](=[CH:6][CH:7]=[CH:8][CH:9]=2)[NH:4][N:3]=1.[O:11]1[CH:16]=[CH:15][CH2:14][CH2:13][CH2:12]1.C(=O)([O-])O.[Na+]>C1(C)C=CC=CC=1.O.C1(C)C=CC(S(O)(=O)=O)=CC=1>[Br:1][C:2]1[C:10]2[C:5](=[CH:6][CH:7]=[CH:8][CH:9]=2)[N:4]([CH:12]2[CH2:13][CH2:14][CH2:15][CH2:16][O:11]2)[N:3]=1

Participants

6

Reactant 3

HCID 80803,4-dihydro-2H-pyranHCID 516892Sodium BicarbonateHCID 178419483HCID 178419483, compound

Product 1

HCID 670597543-bromo-1-(oxan-2-yl)-1H-indazoleYield 79.9%

Reagents, catalysts & solvents 2

HCID 521998p-Toluenesulfonic acid monohydrateCatalystHCID 1140TolueneSolvent

Conditions

Temperature
80 °C

Procedure

To a solution of 3-bromo-1H-indazole (500 mg) synthesized according to a method of the literature (V> Auwers, et al., J. Prakt. Chem., 1924, 314) in toluene (25 mL, manufactured by Wako Pure Chemical Industries, Ltd.), 3,4-dihydro-2H-pyrane (640 mg, manufactured by Tokyo Chemical Industry Co., Ltd.) and p-toluenesulfonic acid monohydrate (10 mg, manufactured by Wako Pure Chemical Industries, Ltd.) were added, and the mixture was heated for one hour at 80° C. The reaction solution was cooled to room temperature, and then a saturated aqueous solution of sodium hydrogen carbonate (10 mL) was added thereto. The mixture was extracted with ethyl acetate (3×20 mL), washed with brine (40 mL), and dried (MgSO4), and the solvent was evaporated. The resulting residue was purified by silica gel column chromatography (hexane:ethyl acetate=9:1), to give 570 mg of the title compound. LC-MS: HPLC retention time 4.93 minutes, m/z 281 (M+H), condition B-1.

Workup

  1. temperatureThe reaction solution was cooled to room temperature
  2. extractionThe mixture was extracted with ethyl acetate (3×20 mL)
  3. washwashed with brine (40 mL)
  4. dry with materialdried (MgSO4)
  5. customthe solvent was evaporated
  6. customThe resulting residue was purified by silica gel column chromatography (hexane:ethyl acetate=9:1)

Sources & evidence

ORD record
ord-b8fc4a30501f4def92effad0546b603a
Source dataset
uspto-grants-2011_08
Patent number
US07994202B2

Reaction notes

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