Cesium carbonate → 2-(4-(6-(Benzyloxy)-4-ethoxypyridin-3-yl)-3-fluorophenyl)acetamide

HRID 576190Notes

Reaction equation

HRID 576190 reaction equation
[F:1][C:2]1[CH:3]=[C:4]([CH2:17][C:18]([NH2:20])=[O:19])[CH:5]=[CH:6][C:7]=1B1OC(C)(C)C(C)(C)O1.[CH2:21]([O:28][C:29]1[CH:34]=[C:33]([O:35][CH2:36][CH3:37])[C:32](I)=[CH:31][N:30]=1)[C:22]1[CH:27]=[CH:26][CH:25]=[CH:24][CH:23]=1.C([O-])([O-])=O.[Cs+].[Cs+]>O1CCOCC1.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]>[CH2:21]([O:28][C:29]1[N:30]=[CH:31][C:32]([C:7]2[CH:6]=[CH:5][C:4]([CH2:17][C:18]([NH2:20])=[O:19])=[CH:3][C:2]=2[F:1])=[C:33]([O:35][CH2:36][CH3:37])[CH:34]=1)[C:22]1[CH:23]=[CH:24][CH:25]=[CH:26][CH:27]=1

Participants

7

Reactant 3

HCID 10796Cesium carbonateHCID 904161632-[3-Fluoro-4-(4,4,5,5-tetramethyl-[1,3,2]dioxaborolan-2-yl)-phenyl]acetamideHCID 904176602-(Benzyloxy)-4-ethoxy-5-iodopyridine

Product 1

HCID 904164292-(4-(6-(Benzyloxy)-4-ethoxypyridin-3-yl)-3-fluorophenyl)acetamideYield 100%

Reagents, catalysts & solvents 3

HCID 178418228Bis(cyclopenta-1,4-dien-1-yl(diphenyl)phosphane);dichloropalladium;iron(2+)CatalystHCID 962WaterSolventHCID 312751,4-DioxaneSolvent

Procedure

A solution of 2-(3-fluoro-4-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)phenyl) acetamide (100 mg, 0.358 mmol), 2-(benzyloxy)-4-ethoxy-5-iodopyridine (127 mg, 0.358 mmol), PdCl2(dppf) (26.2 mg, 0.036 mmol) and Cs2CO3 (233 mg, 0.717 mmol) in 1,4-dioxane (6 mL) and H2O (2 mL) was stirred at 110° C. for 15 min. After LCMS analysis showed the starting material had disappeared, the solvent was removed in vacuo. The residue was dissolved in EA (40 mL) and washed with H2O (20 mL) and brine (20 mL). The organic layer was dried over Na2SO4, filtered and concentrated. The crude product was purified by preparative TLC (PE/EA=1/1) to yield 2-(4-(6-(benzyloxy)-4-ethoxypyridin-3-yl)-3-fluorophenyl)acetamide (20 mg, 0.358 mmol, 14.8% yield): 1H NMR (400 MHz, CD3OD) δ 7.87 (s, 1H), 7.56-7.43 (m, 2H), 7.43-7.22 (m, 4H), 7.21-7.11 (m, 2H), 6.50 (s, 1H), 5.38 (s, 2H), 4.13 (m, 2H), 3.58 (s, 2H), 1.32 (t, J=6.8 Hz, 3H); ES-LCMS m/z 381.1 (M+H).

Workup

  1. customthe solvent was removed in vacuo
  2. dissolutionThe residue was dissolved in EA (40 mL)
  3. washwashed with H2O (20 mL) and brine (20 mL)
  4. dry with materialThe organic layer was dried over Na2SO4
  5. filtrationfiltered
  6. concentrationconcentrated
  7. customThe crude product was purified by preparative TLC (PE/EA=1/1)

Sources & evidence

ORD record
ord-fa3c5ca4123b43b7a58c2b7e59b951db
Source dataset
uspto-grants-2015_05
Patent number
US09035063B2

Reaction notes

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