Isobutyl iodide → HCID 90461169, compound

HRID 1053638Notes

Reaction equation

HRID 1053638 reaction equation
[OH:1][C:2]1[CH:3]=[C:4]2[C:8](=[CH:9][CH:10]=1)[N:7]([CH:11]1[CH2:16][CH2:15][CH2:14][CH2:13][O:12]1)[N:6]=[C:5]2[CH:17]=[O:18].I[CH2:20][CH:21]([CH3:23])[CH3:22].C([O-])([O-])=O.[Cs+].[Cs+]>CN(C)C=O.O>[CH2:20]([O:1][C:2]1[CH:3]=[C:4]2[C:8](=[CH:9][CH:10]=1)[N:7]([CH:11]1[CH2:16][CH2:15][CH2:14][CH2:13][O:12]1)[N:6]=[C:5]2[CH:17]=[O:18])[CH:21]([CH3:23])[CH3:22]

Participants

6

Reactant 3

HCID 10556Isobutyl iodideHCID 10796Cesium carbonateHCID 90460860HCID 90460860, compound

Product 1

HCID 90461169HCID 90461169, compoundYield 67.4%

Reagents, catalysts & solvents 2

HCID 962WaterSolventHCID 6228DimethylformamideSolvent

Conditions

Temperature
70 °C

Procedure

A mixture of (R/S) 5-hydroxy-1-(tetrahydro-2H-pyran-2-yl)-1H-indazole-3-carbaldehyde (200 mg, 0.81 mmol, 1.00 equiv), 1-iodo-2-methylpropane (300 mg, 1.63 mmol, 2.01 equiv) and Cs2CO3 (270 mg, 0.83 mmol, 1.02 equiv) in N,N-dimethylformamide (10 mL) was stirred under nitrogen at 70° C. for 5 h. The resulting solution was cooled to room temperature and diluted with 10 mL of H2O. The mixture was extracted with 3×20 mL of ethyl acetate. The combined organic layers were washed with 3×20 mL of brine, dried over anhydrous sodium sulfate and concentrated under vacuum. The residue was purified on a silica gel column eluted with 0-15% of ethyl acetate in petroleum ether to give 0.165 g (67%) of (R/S) 5-iso-butoxy-1-(tetrahydro-2H-pyran-2-yl)-1H-indazole-3-carbaldehyde as a white solid. 1H-NMR (300 MHz, DMSO-d6): δ 10.16 (s, 1H), 7.83 (d, J=9.3 Hz, 1H), 7.51 (d, J=2.1 Hz, 1H), 7.22 (dd, J=9.3 Hz, 2.4 Hz, 1H), 6.04-6.01 (m, 1H), 4.07-4.00 (m, 1H), 3.92-3.75 (m, 4H), 2.12-2.00 (m, 2H), 1.63-1.62 (m, 2H), 1.24-1.16 (m, 2H), 1.04 (d, J=6.6 Hz, 6H) ppm. LCMS (method A, ESI): RT=1.71 min, m/z=218.9 [M+H−THP]+.

Workup

  1. temperatureThe resulting solution was cooled to room temperature
  2. extractionThe mixture was extracted with 3×20 mL of ethyl acetate
  3. washThe combined organic layers were washed with 3×20 mL of brine
  4. dry with materialdried over anhydrous sodium sulfate
  5. concentrationconcentrated under vacuum
  6. customThe residue was purified on a silica gel column
  7. washeluted with 0-15% of ethyl acetate in petroleum ether

Sources & evidence

ORD record
ord-3560fed9dc4e4e36948942b785f2255f
Source dataset
uspto-grants-2016_07
Patent number
US09394258B2

Reaction notes

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