Cesium carbonate → HCID 178521606, compound

HRID 1020171Notes

Reaction equation

HRID 1020171 reaction equation
F[C:2]1[C:7]([F:8])=[CH:6][C:5]([I:9])=[CH:4][N:3]=1.Cl.[NH2:11][C@H:12]1[CH2:17][CH2:16][C@H:15]([OH:18])[CH2:14][CH2:13]1.C([O-])([O-])=O.[Cs+].[Cs+]>O1CCOCC1>[F:8][C:7]1[C:2]([NH:11][C@H:12]2[CH2:17][CH2:16][C@H:15]([OH:18])[CH2:14][CH2:13]2)=[N:3][CH:4]=[C:5]([I:9])[CH:6]=1

Participants

5

Reactant 3

HCID 10796Cesium carbonateHCID 113224272,3-Difluoro-5-iodopyridineHCID 178479278HCID 178479278, compound

Product 1

HCID 178521606HCID 178521606, compoundYield 16%

Reagents, catalysts & solvents 1

HCID 312751,4-DioxaneSolvent

Conditions

Temperature
100 °C

Procedure

2,3-Difluoro-5-iodopyridine (300 mg, 1.24 mmol) was dissolved in dioxane (3 ml) and trans-4-aminocyclohexanol hydrochloride (227 mg, 1.49 mmol, 1.2 equiv.) and Cs2CO3 (1.01 g, 3.11 mmol, 2.5 equiv.) were added at room temperature. The mixture was stirred for 3 hours at 100° C. The reaction mixture was evaporated and treated with sat. NaHCO3 solution and extracted twice with a small volume of CH2Cl2. The organic layers were loaded directly to silica gel column and the crude material was purified by flash chromatography on silica gel (20 gr, ethyl acetate/heptane gradient, 0:100 to 0:100). The desired trans-4-(3-fluoro-5-iodopyridin-2-ylamino)cyclohexanol (65 mg, 16% yield) was obtained as a white solid, MS: m/e=337.1 (M+H+).

Workup

  1. customThe reaction mixture was evaporated
  2. additiontreated with sat. NaHCO3 solution
  3. extractionextracted twice with a small volume of CH2Cl2
  4. customthe crude material was purified by flash chromatography on silica gel (20 gr, ethyl acetate/heptane gradient, 0:100 to 0:100)

Sources & evidence

ORD record
ord-38bfc9fd52894867bc10e81b736dc829
Source dataset
uspto-grants-2014_05
Patent number
US08716316B2

Reaction notes

Loading…