Potassium Fluoride → HCID 90413471, compound

HRID 1746073Notes

Reaction equation

HRID 1746073 reaction equation
[NH2:1][C:2]1[C:7]([F:8])=[C:6](Cl)[N:5]=[C:4]([C:10]([O:12][CH3:13])=[O:11])[C:3]=1[Cl:14].[O:15]1[C:19]2[CH:20]=[CH:21][CH:22]=[C:23](B3OC(C)(C)C(C)(C)O3)[C:18]=2[O:17][CH2:16]1.[F-].[K+]>C(#N)C.O.C1C=CC(P(C2C=CC=CC=2)C2C=CC=CC=2)=CC=1.C1C=CC(P(C2C=CC=CC=2)C2C=CC=CC=2)=CC=1.Cl[Pd]Cl>[NH2:1][C:2]1[C:7]([F:8])=[C:6]([C:23]2[C:18]3[O:17][CH2:16][O:15][C:19]=3[CH:20]=[CH:21][CH:22]=2)[N:5]=[C:4]([C:10]([O:12][CH3:13])=[O:11])[C:3]=1[Cl:14]

Participants

7

Reactant 3

HCID 522689Potassium FluorideHCID 22677265Methyl 4-amino-3,6-dichloro-5-fluoropicolinateHCID 53217346HCID 53217346, compound

Product 1

HCID 90413471HCID 90413471, compoundYield 68.7%

Reagents, catalysts & solvents 3

HCID 6102075Dichlorobis(triphenylphosphine)palladiumCatalystHCID 962WaterSolventHCID 6342AcetonitrileSolvent

Procedure

Methyl 4-amino-3,6-dichloro-5-fluoropicolinate (1.5 g, 6.28 mmol), 2-(benzo[d][1,3]dioxol-4-yl)-4,4,5,5-tetramethyl-1,3,2-dioxaborolane (2.024 g, 8.16 mmol), potassium fluoride (0.875 g, 15.06 mmol; Note: Related examples utilize cesium fluoride) and bis(triphenylphosphine)palladium(II)chloride (0.440 g, 0.628 mmol) were combined in acetonitrile (13 mL) and water (4.5 mL). The reaction mixture was then irradiated in a microwave at 110° C. in a capped vial for 20 min, with external IR-sensor temperature monitoring from the side of the vessel. The cooled reaction mixture was partitioned between ethyl acetate and water. The organic phase was dried and concentrated onto 1.2 g of silica gel. This mixture was applied to the top of a silica gel column and the product was eluted with a 7-60% hexane/ethyl acetate gradient solvent system to provide the title compound as a white solid (1.4 g, 68.7%): mp 146-148° C.; 1H NMR (400 MHz, CDCl3) δ 7.16-7.09 (m, 1H), 6.98-6.85 (m, 2H), 6.01 (s, 2H), 4.91 (br s, 2H), 3.98 (s, 3H); ESIMS m/z 325 ([M+H]+).

Workup

  1. customThe reaction mixture was then irradiated in a microwave at 110° C. in a capped vial for 20 min
  2. customThe cooled reaction mixture
  3. customwas partitioned between ethyl acetate and water
  4. customThe organic phase was dried
  5. concentrationconcentrated onto 1.2 g of silica gel
  6. washthe product was eluted with a 7-60% hexane/ethyl acetate gradient solvent system

Sources & evidence

ORD record
ord-cbaaef7a0f42428a9a13a71e4da12963
Source dataset
uspto-grants-2015_10
Patent number
US09149038B2

Reaction notes

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