Ethyl bromoacetate → Ethyl [3-(2,2-dimethylpropanoyl)-6-methoxy-1H-indazol-1-yl]acetate

HRID 490791Notes

Reaction equation

HRID 490791 reaction equation
[CH3:1][O:2][C:3]1[CH:11]=[C:10]2[C:6]([C:7]([C:12](=[O:17])[C:13]([CH3:16])([CH3:15])[CH3:14])=[N:8][NH:9]2)=[CH:5][CH:4]=1.Br[CH2:19][C:20]([O:22][CH2:23][CH3:24])=[O:21].C(=O)([O-])[O-].[Cs+].[Cs+]>CN(C=O)C.CCOCC.O.Cl>[CH3:15][C:13]([CH3:14])([CH3:16])[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]([CH2:19][C:20]([O:22][CH2:23][CH3:24])=[O:21])[N:8]=1)=[O:17]

Participants

8

Reactant 3

HCID 7748Ethyl bromoacetateHCID 10796Cesium carbonateHCID 57675519(6-methoxy-1H-indazol-3-yl)-2,2-dimethylpropan-1-one

Product 1

HCID 57675509Ethyl [3-(2,2-dimethylpropanoyl)-6-methoxy-1H-indazol-1-yl]acetate

Reagents, catalysts & solvents 4

HCID 313Hydrochloric AcidSolventHCID 962WaterSolventHCID 3283Diethyl EtherSolventHCID 6228DimethylformamideSolvent

Procedure

To a solution of 1.43 g (6-methoxy-1H-indazol-3-yl)-2,2-dimethylpropan-1-one from the Step C above in 45 mL anhydrous DMF was added 1.13 g ethyl bromoacetate and 2.41 g cesium carbonate. The mixture was stirred under nitrogen at room temperature for 2.5 days. It was diluted with ether and cold water with 15 mL 1 N HCl. The aqueous layer was separated and extracted with ether three times. The combined ether extract was washed with water (5×) and saturated brine, dried over anhydrous Na2SO4 and evaporated to give a crude product. It was purified by SGC with 20-40% EtOAc in hexanes to give title compound as solid. 1H NMR (CDCl3, 500 MHz) δ 8.27 (d, J=8.9 Hz, 1H), 6.985 (dd, J=2.1 & 8.9 Hz, 1H), 6.68 (d, J=2.0 Hz, 1H), 5.15 (s, 2H), 4.27 (q, J=7.1 Hz, 2H), 3.90 (s, 3H), 1.50 (s, 9H), 1.28 (t, J=7.1 Hz, 3H). LC-MS: 3.93 min. (m/Z=319.3).

Workup

  1. customThe aqueous layer was separated
  2. extractionextracted with ether three times
  3. extractionThe combined ether extract
  4. washwas washed with water (5×) and saturated brine
  5. dry with materialdried over anhydrous Na2SO4
  6. customevaporated
  7. customto give a crude product
  8. customIt was purified by SGC with 20-40% EtOAc in hexanes

Sources & evidence

ORD record
ord-0d841d897b9c4645bc3fd69a7c386923
Source dataset
uspto-grants-2009_05
Patent number
US07528163B2

Reaction notes

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