Cesium carbonate → 4-Iodo-1-[2-(tetrahydro-pyran-2-yloxy)-ethyl]-1H-pyrazole-3-carboxylic acid ethyl ester
Reaction equation
[CH2:1]([O:3][C:4]([C:6]1[C:10]([I:11])=[CH:9][NH:8][N:7]=1)=[O:5])[CH3:2].C(=O)([O-])[O-].[Cs+].[Cs+].Br[CH2:19][CH2:20][O:21][CH:22]1[CH2:27][CH2:26][CH2:25][CH2:24][O:23]1>C(#N)C>[CH2:1]([O:3][C:4]([C:6]1[C:10]([I:11])=[CH:9][N:8]([CH2:19][CH2:20][O:21][CH:22]2[CH2:27][CH2:26][CH2:25][CH2:24][O:23]2)[N:7]=1)=[O:5])[CH3:2]Participants
Procedure
A suspension of Intermediate 74b (2.72 g, 10.2 mmol) in acetonitrile (27 mL) was treated with caesium carbonate (5.0 g, 15.3 mmol) then 2-(2-bromoethoxy)tetrahydro-2H-pyran (1.70 mL, 11.2 mmol) and the mixture was stirred at 60° C. for 3.5 h. The mixture was evaporated in vacuo and the residue was partitioned between EtOAc and water. The aqueous layer was then extracted with EtOAc (2×). The combined organic layers were washed with saturated aqueous sodium bicarbonate solution and brine, dried (Na2SO4), filtered and evaporated in vacuo. The residue was purified by FCC, using 0-50% EtOAc in cyclohexane, isolating the lower running spot to give the title compound as a colourless glass (1.57 g, 39%). LCMS (Method 3): Rt 3.67 min, m/z 417 [M+Na+].
Workup
- customThe mixture was evaporated in vacuo
- customthe residue was partitioned between EtOAc and water
- extractionThe aqueous layer was then extracted with EtOAc (2×)
- washThe combined organic layers were washed with saturated aqueous sodium bicarbonate solution and brine
- dry with materialdried (Na2SO4)
- filtrationfiltered
- customevaporated in vacuo
- customThe residue was purified by FCC
- customisolating the
Sources & evidence
- ORD record
- ord-109ef76845af46d98c5cfdefc68fce01
- Source dataset
- uspto-grants-2016_09
- Patent number
- US09440974B2
Reaction notes
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