L-Hydroxyproline → HCID 64176736, compound

HRID 537422Notes

Reaction equation

HRID 537422 reaction equation
I[C:2]1[CH:7]=[CH:6][C:5]([CH2:8][OH:9])=[CH:4][CH:3]=1.[F:10][C:11]([F:18])([F:17])[C:12]1[CH:13]=[N:14][NH:15][CH:16]=1.O[C@H]1CN[C@H](C(O)=O)C1.C(=O)([O-])[O-].[Cs+].[Cs+]>CS(C)=O.O.[Cu]I>[F:10][C:11]([F:18])([F:17])[C:12]1[CH:13]=[N:14][N:15]([C:2]2[CH:7]=[CH:6][C:5]([CH2:8][OH:9])=[CH:4][CH:3]=2)[CH:16]=1

Participants

8

Reactant 4

HCID 5810L-HydroxyprolineHCID 10796Cesium carbonateHCID 290124-Iodobenzyl alcoholHCID 127777954-(Trifluoromethyl)-1H-pyrazole

Product 1

HCID 64176736HCID 64176736, compound

Reagents, catalysts & solvents 3

HCID 24350Copper(1+) iodide; Copper(I) iodide; Cuprous iodide; Cuprous iodide (CuI)CatalystHCID 679Dimethyl SulfoxideSolventHCID 962WaterSolvent

Conditions

Temperature
85 °C

Procedure

A mixture of (4-iodophenyl)methanol (1030 mg, 4.41 mmol), 4-(trifluoromethyl)-1H-pyrazole (600 mg, 4.41 mmol), copper(I) iodide (168 mg, 0.882 mmol), trans-4-hydroxy-L-proline (231 mg, 1.76 mmol) and cesium carbonate (2900 mg, 8.82 mmol) in dimethylsulfoxide (7.5 mL) was heated to 85° C. for 20 hours. The mixture was diluted with water and extracted with ethyl acetate twice. The combined organic layers were dried over sodium sulfate, filtered and concentrated. Purification by column chromatography (0-45% ethyl acetate in heptane), gave (4-(4-(trifluoromethyl)-1H-pyrazol-1-yl)phenyl)methanol. 1H NMR (400 MHz, CDCl3, δ): 8.16 (s, 1H), 7.89 (s, 1H), 7.65 (d, J=8.39 Hz, 2H), 7.47 (d, J=8.39 Hz, 2H), 4.74 (d, J=5.66 Hz, 2H), 1.85 (t, J=5.86 Hz, 1H).

Workup

  1. extractionextracted with ethyl acetate twice
  2. dry with materialThe combined organic layers were dried over sodium sulfate
  3. filtrationfiltered
  4. concentrationconcentrated
  5. customPurification by column chromatography (0-45% ethyl acetate in heptane)

Sources & evidence

ORD record
ord-ab617a45f7d349178c177d3041ee82ef
Source dataset
uspto-grants-2014_10
Patent number
US08859591B2

Reaction notes

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