Cesium carbonate → tert-Butyl (2-chloro-5-fluoropyridin-4-yl)carbamate

HRID 2171255Notes

Reaction equation

HRID 2171255 reaction equation
[C:1](=[O:8])([O:3][C:4]([CH3:7])([CH3:6])[CH3:5])[NH2:2].C(=O)([O-])[O-].[Cs+].[Cs+].CC1(C)C2C(=C(P(C3C=CC=CC=3)C3C=CC=CC=3)C=CC=2)OC2C(P(C3C=CC=CC=3)C3C=CC=CC=3)=CC=CC1=2.[Cl:57][C:58]1[CH:63]=[C:62](I)[C:61]([F:65])=[CH:60][N:59]=1>C1C=CC(/C=C/C(/C=C/C2C=CC=CC=2)=O)=CC=1.C1C=CC(/C=C/C(/C=C/C2C=CC=CC=2)=O)=CC=1.C1C=CC(/C=C/C(/C=C/C2C=CC=CC=2)=O)=CC=1.[Pd].[Pd].O.C1(C)C=CC=CC=1>[Cl:57][C:58]1[CH:63]=[C:62]([NH:2][C:1](=[O:8])[O:3][C:4]([CH3:7])([CH3:6])[CH3:5])[C:61]([F:65])=[CH:60][N:59]=1

Participants

8

Reactant 4

HCID 10796Cesium carbonateHCID 77922tert-Butyl carbamateHCID 6360441,1'-(9,9-Dimethyl-9H-xanthene-4,5-diyl)bis(1,1-diphenylphosphine)HCID 248204952-Chloro-5-fluoro-4-iodopyridine

Product 1

HCID 71741530tert-Butyl (2-chloro-5-fluoropyridin-4-yl)carbamateYield 79.8%

Reagents, catalysts & solvents 3

HCID 9811564Bis(dibenzylideneacetone)palladiumCatalystHCID 962WaterSolventHCID 1140TolueneSolvent

Conditions

Temperature
100 °C

Procedure

tert-Butyl carbamate (960 mg), cesium carbonate (5.06 g), Pd2(dba)3 (1.07 g), and Xantphos (1.35 g) were added to a toluene solution (40 ml) containing 2-chloro-5-fluoro-4-iodopyridine (2 g), followed by stirring at 100° C. for 3 hours. The reaction solution was adjusted to room temperature and water was added to the reaction solution, followed by extraction with ethyl acetate. The organic layers were washed with saturated saline and dried over anhydrous sodium sulfate. The solvent was distilled away under reduced pressure and the obtained residue was purified by silica gel chromatography (n-hexane:ethyl acetate=9:1 to 4:1). A yellow oily matter of tert-butyl (2-chloro-5-fluoropyridin-4-yl)carbamate (1.53 g) was thus obtained.

Workup

  1. customwas adjusted to room temperature
  2. extractionfollowed by extraction with ethyl acetate
  3. washThe organic layers were washed with saturated saline
  4. dry with materialdried over anhydrous sodium sulfate
  5. distillationThe solvent was distilled away under reduced pressure
  6. customthe obtained residue was purified by silica gel chromatography (n-hexane:ethyl acetate=9:1 to 4:1)

Sources & evidence

ORD record
ord-03c91063e62a4b90ac9c3ff8a207582d
Source dataset
uspto-grants-2015_06
Patent number
US09051310B2

Reaction notes

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