Ethyl chloroacetate → ethyl (5-nitro-1-tetrahydro-2H-pyran-2-yl-1H-indazol-4-yl)acetate

HRID 1269872Notes

Reaction equation

HRID 1269872 reaction equation
CC(C)([O-])C.[K+].[N+:7]([C:10]1[CH:11]=[C:12]2[C:16](=[CH:17][CH:18]=1)[N:15]([CH:19]1[CH2:24][CH2:23][CH2:22][CH2:21][O:20]1)[N:14]=[CH:13]2)([O-:9])=[O:8].Cl.NC1C(C)=CC(C(OC)=O)=C(C)C=1.Cl[CH2:40][C:41]([O:43][CH2:44][CH3:45])=[O:42]>O1CCCC1>[CH2:44]([O:43][C:41](=[O:42])[CH2:40][C:11]1[C:10]([N+:7]([O-:9])=[O:8])=[CH:18][CH:17]=[C:16]2[C:12]=1[CH:13]=[N:14][N:15]2[CH:19]1[CH2:24][CH2:23][CH2:22][CH2:21][O:20]1)[CH3:45]

Participants

6

Reactant 4

HCID 7751Ethyl chloroacetateHCID 151476265-Nitro-1-(tetrahydro-2H-pyran-2-yl)-1H-indazoleHCID 22933657Methyl 4-amino-2,5-dimethylbenzoate hydrochlorideHCID 23665647Potassium tert-butoxide

Product 1

HCID 86593613ethyl (5-nitro-1-tetrahydro-2H-pyran-2-yl-1H-indazol-4-yl)acetateYield 78%

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent2×

Conditions

Temperature
-40 °C

Procedure

A solution of potassium tert-butoxide (2.02 g, 18.0 mmol) in tetrahydrofuran (20 ml) was added dropwise to a solution of the 5-nitro-1-tetrahydro-2H-pyran-2-yl-1H-indazole (1.85 g, 7.48 mmol) obtained in Example 317, (d) and ethyl chloroacetate (960 μl, 9.01 mmol) in tetrahydrofuran (10 ml) at −40° C. over a period of 15 minutes, and stirred at −40° C. for 1 hour. The reaction was terminated by pouring 1N-hydrochloric acid, and the reaction solution was extracted with ethyl acetate. The extract solution was washed with a saturated aqueous sodium chloride solution, dried over sodium sulfate, and then distilled under reduced pressure to remove the solvent, whereby a crude product was obtained. The crude product was purified by a silica gel column chromatography (eluent: hexane/ethyl acetate=4/1) to obtain ethyl(5-nitro-1-tetrahydro-2H-pyran-2-yl-1H-indazol-4-yl)acetate (1.93 g, 78%).

Workup

  1. customThe reaction was terminated
  2. additionby pouring 1N-hydrochloric acid
  3. extractionthe reaction solution was extracted with ethyl acetate
  4. washThe extract solution was washed with a saturated aqueous sodium chloride solution
  5. dry with materialdried over sodium sulfate
  6. distillationdistilled under reduced pressure
  7. customto remove the solvent, whereby a crude product
  8. customwas obtained
  9. customThe crude product was purified by a silica gel column chromatography (eluent: hexane/ethyl acetate=4/1)

Sources & evidence

ORD record
ord-f368dba48dd646f481792908d32d4e0e
Source dataset
uspto-grants-2007_04
Patent number
US07199147B2

Reaction notes

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