4-Fluorophenylacetyl chloride → HCID 25197077, compound

HRID 2373971Notes

Reaction equation

HRID 2373971 reaction equation
FC1C=CC(CC(Cl)=O)=CC=1.[F:12][C:13]1[CH:18]=[CH:17][C:16]([CH2:19][C:20]([N:22]=[C:23]=[O:24])=[O:21])=[CH:15][CH:14]=1.[F:25][C:26]1[CH:27]=[C:28]([NH2:39])[CH:29]=[CH:30][C:31]=1[O:32][C:33]1[CH:38]=[CH:37][N:36]=[CH:35][CH:34]=1>C1(C)C=CC=CC=1.C(Cl)Cl.[Ag]OC#N>[F:25][C:26]1[CH:27]=[C:28]([NH:39][C:23]([NH:22][C:20](=[O:21])[CH2:19][C:16]2[CH:15]=[CH:14][C:13]([F:12])=[CH:18][CH:17]=2)=[O:24])[CH:29]=[CH:30][C:31]=1[O:32][C:33]1[CH:34]=[CH:35][N:36]=[CH:37][CH:38]=1

Participants

7

Reactant 3

HCID 37449884-Fluorophenylacetyl chlorideHCID 231530882-(4-Fluorophenyl)acetyl isocyanateHCID 43259379HCID 43259379, compound

Product 1

HCID 25197077HCID 25197077, compoundYield 46%

Reagents, catalysts & solvents 3

HCID 178513473HCID 178513473, compoundCatalystHCID 1140TolueneSolventHCID 6344DichloromethaneSolvent

Procedure

Silver cyanate (0.912 g, 6.08 mmol, 1.05 eq) was added to a solution of 4-fluorophenylacetyl chloride (Aldrich, 0.794 mL, 5.79 mmol, 1.0 eq) in toluene (16 mL) at room temperature shielded from light. The reaction mixture was heated to reflux for 60 minutes and then cooled to room temperature. The reaction mixture was filtered (Acrodisc, PTFE 0.2 μM) and the resultant 2-(4-fluorophenyl)acetyl isocyanate solution (0.36 M, 0.75 mL, 0.27 mmol, 1.1 eq) was added to a solution of 3-fluoro-4-(pyridin-4-yloxy)benzenamine (0.050 g, 0.245 mmol, 1.0 eq) in CH2Cl2 (2.0 mL) at room temperature. The reaction mixture was stirred at room temperature for 1 h, quenched with saturated aqueous NaCl solution and the mixture was extracted with CH2Cl2 (3×30 mL). The combined organic extracts were dried (Na2SO4), filtered and concentrated in vacuo. The residue was purified by silica gel flash chromatography (Merck, 40-63 μM, 230-240 mesh, eluting 0-5% MeOH in CHCl3) to afford the title compound (0.043 g, 46%) as a solid. 1H NMR (DMSO-d6) δ 11.06 (s, 1H), 10.60 (s, 1H), 8.47 (s, 2H), 7.77-7.80 (m, 1H), 6.92-7.48 (m, 8H), 3.75 (s, 2H); MS(ESI+) m/z 384 (M+H)+; HRMS(ESI+) calcd.: 384.1160, found: 384.1147.

Workup

  1. temperatureThe reaction mixture was heated
  2. temperatureto reflux for 60 minutes
  3. filtrationThe reaction mixture was filtered (Acrodisc, PTFE 0.2 μM)
  4. customquenched with saturated aqueous NaCl solution
  5. extractionthe mixture was extracted with CH2Cl2 (3×30 mL)
  6. dry with materialThe combined organic extracts were dried (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 0-5% MeOH in CHCl3)

Sources & evidence

ORD record
ord-0309c0b3bc3f42ba9b9bbaa113fa606a
Source dataset
uspto-grants-2008_12
Patent number
US07459562B2

Reaction notes

Loading…