Sodium thiocyanate → 2-(4-Fluorophenyl)acetyl isothiocyanate

HRID 2373979Notes

Reaction equation

HRID 2373979 reaction equation
[F:1][C:2]1[CH:7]=[CH:6][C:5]([CH2:8][C:9](Cl)=[O:10])=[CH:4][CH:3]=1.[S-:12][C:13]#[N:14].[Na+]>C(OCC)(=O)C>[F:1][C:2]1[CH:7]=[CH:6][C:5]([CH2:8][C:9]([N:14]=[C:13]=[S:12])=[O:10])=[CH:4][CH:3]=1

Participants

4

Reactant 2

HCID 516871Sodium thiocyanateHCID 37449884-Fluorophenylacetyl chloride

Product 1

HCID 231532482-(4-Fluorophenyl)acetyl isothiocyanate

Reagents, catalysts & solvents 1

HCID 8857Ethyl AcetateSolvent

Procedure

4-Fluorophenylacetylchloride (Aldrich, 0.017 mL, 0.126 mmol, 2.5 eq) was added to a solution of sodium thiocyanate (0.014 g, 0.176 mmol, 3.5 eq) in ethyl acetate (1.0 mL) at room temperature and the reaction mixture was stirred for 1.5 h to afford a 2-(4-fluorophenyl)ethanoyl isothiocyanate solution (0.126 M). 4-(4-Amino-2-fluorophenoxy)pyridin-2-amine (Compound B of Example 24, 0.011 g, 0.050 mmol, 1.0 eq) was dissolved in CH2Cl2 (1.0 mL) and 2-(4-fluorophenyl)ethanoyl isothiocyanate (0.126 M, 0.50 mL, 0.063 mmol, 1.3 eq) was added and the reaction mixture was stirred at room temperature for 20 h. The reaction mixture was concentrated in vacuo and the resulting residue was purified by silica gel flash chromatography (Merck, 40-63 μM, 230-240 mesh, eluting 0-6% MeOH in CHCl3) to afford the title compound (0.008 g, 38%) as a solid. 1H NMR (CD3OD) δ 7.85-7.95 (m, 1H), 7.67-7.69 (m, 1H), 7.13-7.28 (m, 4H), 6.95-7.00 (m, 2H), 6.05-6.15 (m, 1H), 5.90-5.91 (m, 1H), 3.65 (s, 2H); MS(ESI+) m/z 415 (M+H)+; HRMS(ESI+) calculated: 415.1040, found: 415.1041.

Sources & evidence

ORD record
ord-35ecdb8527ae4b29804d5031112fbcad
Source dataset
uspto-grants-2008_12
Patent number
US07459562B2

Reaction notes

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