Water → HCID 60209930, compound

HRID 1497338Notes

Reaction equation

HRID 1497338 reaction equation
[F:1][C:2]1[CH:3]=[CH:4][CH:5]=[C:6]2[C:11]=1[N:10]=[C:9]([C:12]([O:14][CH3:15])=[O:13])[CH:8]=[C:7]2B1OC(C)(C)C(C)(C)O1.C([O-])([O-])=O.[Cs+].[Cs+].Cl[CH2:32][C:33]1[CH:38]=[CH:37][N:36]=[C:35]([O:39][CH3:40])[CH:34]=1.O>C1COCC1.CCOC(C)=O.C1C=CC(P(C2C=CC=CC=2)[C-]2C=CC=C2)=CC=1.C1C=CC(P(C2C=CC=CC=2)[C-]2C=CC=C2)=CC=1.Cl[Pd]Cl.[Fe+2].C(Cl)Cl>[F:1][C:2]1[CH:3]=[CH:4][CH:5]=[C:6]2[C:11]=1[N:10]=[C:9]([C:12]([O:14][CH3:15])=[O:13])[CH:8]=[C:7]2[CH2:32][C:33]1[CH:38]=[CH:37][N:36]=[C:35]([O:39][CH3:40])[CH:34]=1

Participants

8

Reactant 4

HCID 962WaterHCID 10796Cesium carbonateHCID 179484394-(Chloromethyl)-2-methoxypyridineHCID 60209927HCID 60209927, compound

Product 1

HCID 60209930HCID 60209930, compound

Reagents, catalysts & solvents 3

HCID 178418807HCID 178418807, compoundCatalystHCID 8028TetrahydrofuranSolventHCID 8857Ethyl AcetateSolvent

Conditions

Temperature
100 °C

Procedure

To a mixture of methyl 8-fluoro-4-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)quinoline-2-carboxylate (S1) (130 mg, 0.393 mmol), Cs2CO3 (384 mg, 1.178 mmol), PdCl2(dppf)-CH2Cl2 adduct (32.1 mg, 0.039 mmol) in a microwave tube were added a solution of 4-(chloromethyl)-2-methoxypyridine (124 mg, 0.785 mmol) in THF (3 mL) followed by adding water (0.3 mL). The mixture was heated at 100° C. for 1 h. The reaction was cooled and diluted with EtOAc. The bottom H2O layer was removed. The organic layer was dried over Na2SO4, filtered and concentrated. The residue was purified by reverse-phase HPLC (C-18 column, gradient 5-90% MeCN in H2O with both containing 0.05% TFA) to give methyl 8-fluoro-4-[(2-methoxypyridin-4-yl)methyl]quinoline-2-carboxylate (V4). ES-MS [M+1]+: 327.2.

Workup

  1. temperatureThe reaction was cooled
  2. customThe bottom H2O layer was removed
  3. dry with materialThe organic layer was dried over Na2SO4
  4. filtrationfiltered
  5. concentrationconcentrated
  6. customThe residue was purified by reverse-phase HPLC (C-18 column, gradient 5-90% MeCN in H2O with both containing 0.05% TFA)

Sources & evidence

ORD record
ord-02a5903297c2408e8e69cd5d00a58633
Source dataset
uspto-grants-2015_12
Patent number
US09199939B2

Reaction notes

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