Propyne → 2-isopropoxy-3-methoxy-6-(prop-1-ynyl)-N-trifluoroacetylaniline

HRID 1020499Notes

Reaction equation

HRID 1020499 reaction equation
I[C:2]1[C:7]([NH:8][C:9](=[O:14])[C:10]([F:13])([F:12])[F:11])=[C:6]([O:15][CH:16]([CH3:18])[CH3:17])[C:5]([O:19][CH3:20])=[CH:4][CH:3]=1.[CH:21](N(CC)C(C)C)([CH3:23])[CH3:22].C#CC>CN(C=O)C.[Cu]I>[CH:16]([O:15][C:6]1[C:5]([O:19][CH3:20])=[CH:4][CH:3]=[C:2]([C:22]#[C:21][CH3:23])[C:7]=1[NH:8][C:9](=[O:14])[C:10]([F:13])([F:12])[F:11])([CH3:18])[CH3:17]

Participants

6

Reactant 3

HCID 6335PropyneHCID 81531DiisopropylethylamineHCID 866376576-iodo-2-isopropoxy-3-methoxy-N-trifluoroacetylaniline

Product 1

HCID 866376562-isopropoxy-3-methoxy-6-(prop-1-ynyl)-N-trifluoroacetylanilineYield 79%

Reagents, catalysts & solvents 2

HCID 24350Copper(1+) iodide; Copper(I) iodide; Cuprous iodide; Cuprous iodide (CuI)CatalystHCID 6228DimethylformamideSolvent

Procedure

A mixture of the product of Step B (0.275 g; 0.681 mmol), Cl2Pd(PPh3)2 (0.058 g; 0.083 mmol); CuI (0.025 g; 0.13 μmol), anhydrous N,N-diisopropyl ethylamine (1 ml) in anhydrous DMF (5 ml) was cooled to −40° C., degassed under reduced pressure and saturated with dry N2. To it, propyne gas (0.5 g; 12.4 mmol) was added at −40° C. The reaction flask was sealed with septum and allowed to warm up to room temperature and stirred overnight at room temperature than evaporated to dryness under reduced pressure. The residue was purified by flash column chromatography (SiO2, hexane/ethyl acetate, 8:2) to give the title compound (0.171 g; 79% yield) as creamy solid. 1H-NMR (CDCl3) 1.21 (d, 6H, J=6.16 Hz); 2.00 (s, 3H); 3.86 (s, 3H); 4.43 (m, 1H, J=6.16 Hz); 6.79 (d, 1H, J=8.67 Hz); 7.14 (d, 1H, J=8.67 Hz); 7.72 (broad s, 1H).

Workup

  1. customdegassed under reduced pressure and saturated with dry N2
  2. customThe reaction flask was sealed with septum
  3. customthan evaporated to dryness under reduced pressure
  4. customThe residue was purified by flash column chromatography (SiO2, hexane/ethyl acetate, 8:2)

Sources & evidence

ORD record
ord-b986d80882f642a9ab55dd1ede126749
Source dataset
uspto-grants-2014_05
Patent number
US08716335B2

Reaction notes

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