Ethyl bromoacetate → Ethyl (3-isobutyryl-6-methoxy-1H-indazol-1-yl)acetate

HRID 229458Notes

Reaction equation

HRID 229458 reaction equation
[CH3:1][O:2][C:3]1[CH:11]=[C:10]2[C:6]([C:7]([C:12](=[O:16])[CH:13]([CH3:15])[CH3:14])=[N:8][NH:9]2)=[CH:5][CH:4]=1.Br[CH2:18][C:19]([O:21][CH2:22][CH3:23])=[O:20].CCOC(C)=O>CN(C=O)C.C(=O)([O-])[O-].[Cs+].[Cs+]>[C:12]([C:7]1[C:6]2[C:10](=[CH:11][C:3]([O:2][CH3:1])=[CH:4][CH:5]=2)[N:9]([CH2:18][C:19]([O:21][CH2:22][CH3:23])=[O:20])[N:8]=1)(=[O:16])[CH:13]([CH3:14])[CH3:15]

Participants

6

Reactant 3

HCID 7748Ethyl bromoacetateHCID 8857Ethyl AcetateHCID 588238251-(6-methoxy-1H-indazol-3-yl)-2-methylpropan-1-one

Product 1

HCID 86618180Ethyl (3-isobutyryl-6-methoxy-1H-indazol-1-yl)acetate

Reagents, catalysts & solvents 2

HCID 6228DimethylformamideSolventHCID 10796Cesium carbonateSolvent

Procedure

Dissolve 5.456 g of 1-(6-methoxy-1H-indazol-3-yl)-2-methylpropan-1-one in 100 mL anhydrous DMF. Weigh in 8.96 g cesium carbonate followed by 4.593 g ethyl bromoacetate. The resulting mixture was stirred at room temperature overnight. The solvent was removed under reduced pressure. Partition the residue between EtOAc and water. Extract the aqueous layer with EtOAc several times. The combined organic extract was washed with water (3×) and saturated brine, dried over anhydrous Na2SO4, and evaporated to give the crude product. The title compound was obtained by recrystallization from 40 mL 4:1 hexanes and EtOAc. 1H NMR (CDCl3, 500 MHz) δ 8.26 (d, 8.9 Hz, 1H), 7.00 (dd, 2.1 & 9.0 Hz, 1H), 6.685 (d, 2.1 Hz, 1H), 5.17 (s, 2H), 4.28 (q, 7.1 Hz, 2H), 3.90 (s, 3H), 3.87 (heptet, 6.9 Hz, 1H), 1.29 (t, 7.1 Hz, 3H), 1.28 (d, 6.8 Hz, 6H). LC-MS: 3.51 min. (m/Z=305.1, 327.0).

Workup

  1. customThe solvent was removed under reduced pressure
  2. customPartition the residue between EtOAc and water
  3. extractionExtract the aqueous layer with EtOAc several times
  4. extractionThe combined organic extract
  5. washwas washed with water (3×) and saturated brine
  6. dry with materialdried over anhydrous Na2SO4
  7. customevaporated
  8. customto give the crude product

Sources & evidence

ORD record
ord-61b7c45b7a3d44cc8f95aa2962e2dba1
Source dataset
uspto-grants-2009_07
Patent number
US07563816B2

Reaction notes

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