Benzylamine → HCID 59852895, compound

HRID 1670221Notes

Reaction equation

HRID 1670221 reaction equation
Cl[C:2]1[CH:7]=[C:6]([O:8][C:9]2[CH:14]=[CH:13][C:12]([NH:15][C:16](=[O:22])[O:17][C:18]([CH3:21])([CH3:20])[CH3:19])=[CH:11][C:10]=2[F:23])[CH:5]=[CH:4][N:3]=1.CC([O-])(C)C.[Na+].[CH2:30]([NH2:37])[C:31]1[CH:36]=[CH:35][CH:34]=[CH:33][CH:32]=1>C1(C)C=CC=CC=1.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.[Fe+2].Cl[Pd]Cl>[C:18]([O:17][C:16](=[O:22])[NH:15][C:12]1[CH:13]=[CH:14][C:9]([O:8][C:6]2[CH:5]=[CH:4][N:3]=[C:2]([NH:37][CH2:30][C:31]3[CH:36]=[CH:35][CH:34]=[CH:33][CH:32]=3)[CH:7]=2)=[C:10]([F:23])[CH:11]=1)([CH3:21])([CH3:20])[CH3:19]

Participants

7

Reactant 3

HCID 7504BenzylamineHCID 23676156Sodium t-butoxideHCID 59852942HCID 59852942, compound

Product 1

HCID 59852895HCID 59852895, compoundYield 17%

Reagents, catalysts & solvents 3

HCID 24290Palladium ChlorideCatalystHCID 635956Ferrocene-1,1'-bis-(diphenylphosphine)Catalyst2×HCID 1140TolueneSolvent

Conditions

Temperature
80 °C

Procedure

tert-Butyl 4-(2-chloropyridin-4-yloxy)-3-fluorophenylcarbamate (0.100 g, 0.295 mmol, 1.0 eq) was added to a degassed solution of dppf.PdCl2 (Matrix Scientific, 0.011 g, 0.0148 mmol, 0.05 eq), dppf (0.012 g, 0.022 mmol, 0.075 eq), and NaOt-Bu (0.040 g, 0.414 mmol, 1.4 eq) in toluene at room temperature. Benzylamine (0.045 mL, 0.414 mmol, 1.4 eq) was added to the reaction mixture and the resulting solution was stirred at 80° C. for 4 h. The reaction mixture was cooled to room temperature, quenched with 1N HCl and the solution extracted with CHCl3 (3×50 mL). The combined organic extracts were washed with 1 N NaOH (70 mL), dried (Na2SO4), filtered and concentrated in vacuo. The residue was purified by silica gel flash chromatography (Merck, 40-63 μM, 230-240 mesh, eluting 2:1 hexane/ethyl acetate) to afford the title compound (0.020 g, 17%). 1H NMR (CDCl3) δ 7.80-7.90 (m, 1H), 7.35-7.45 (m, 1H), 7.19-7.24 (m, 3H), 6.91-6.93 (m, 2H), 6.59 (br m, 1H), 6.10-6.20 (m, 1H), 5.75 (br m, 1H), 5.30-5.40 (m, 1H), 4.34 (s, 2H), 1.46 (s, 9H); MS (ESI+) m/z 410 (M+H)+; HRMS (ESI+) calcd.: 410.1880. found: 410.1884.

Workup

  1. customat room temperature
  2. temperatureThe reaction mixture was cooled to room temperature
  3. customquenched with 1N HCl
  4. extractionthe solution extracted with CHCl3 (3×50 mL)
  5. washThe combined organic extracts were washed with 1 N NaOH (70 mL)
  6. dry with materialdried (Na2SO4)
  7. filtrationfiltered
  8. concentrationconcentrated in vacuo
  9. customThe residue was purified by silica gel flash chromatography (Merck, 40-63 μM, 230-240 mesh, eluting 2:1 hexane/ethyl acetate)

Sources & evidence

ORD record
ord-8dffe72bd3dd4473b307f892a4bbc2f3
Source dataset
uspto-grants-2011_08
Patent number
US07989477B2

Reaction notes

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