Diisopropylamine → 2-(2-Chlorophenylamino)-3,4-difluoro-6-trimethylsilanylethynylbenzoic acid methyl ester

HRID 1723681Notes

Reaction equation

HRID 1723681 reaction equation
[CH3:1][O:2][C:3](=[O:21])[C:4]1[C:9](Br)=[CH:8][C:7]([F:11])=[C:6]([F:12])[C:5]=1[NH:13][C:14]1[CH:19]=[CH:18][CH:17]=[CH:16][C:15]=1[Cl:20].[Si:22]([C:26]#[CH:27])([CH3:25])([CH3:24])[CH3:23].N(C(C)C)C(C)C>C1COCC1.Cl[Pd](Cl)([P](C1C=CC=CC=1)(C1C=CC=CC=1)C1C=CC=CC=1)[P](C1C=CC=CC=1)(C1C=CC=CC=1)C1C=CC=CC=1.[Cu]I>[CH3:1][O:2][C:3](=[O:21])[C:4]1[C:9]([C:27]#[C:26][Si:22]([CH3:25])([CH3:24])[CH3:23])=[CH:8][C:7]([F:11])=[C:6]([F:12])[C:5]=1[NH:13][C:14]1[CH:19]=[CH:18][CH:17]=[CH:16][C:15]=1[Cl:20]

Participants

7

Reactant 3

HCID 7912DiisopropylamineHCID 66111TrimethylsilylacetyleneHCID 865985926-Bromo-2-(2-chlorophenylamino)-3,4-difluorobenzoic acid methyl ester

Product 1

HCID 865985932-(2-Chlorophenylamino)-3,4-difluoro-6-trimethylsilanylethynylbenzoic acid methyl esterYield 79%

Reagents, catalysts & solvents 3

HCID 24350Copper(1+) iodide; Copper(I) iodide; Cuprous iodide; Cuprous iodide (CuI)CatalystHCID 178418476HCID 178418476, compoundCatalystHCID 8028TetrahydrofuranSolvent

Procedure

A mixture of 6-bromo-2-(2-chlorophenylamino)-3,4-difluorobenzoic acid methyl ester (2.61 g, 6.93 mmol), TMS-acetylene (1.18 mL, 8.32 mmol), Pd(PPh3)2Cl2 (496 mg, 0.693 mmol), CuI (132 mg, 0.693 mmol), and i-Pr2NH (1.95 mL, 13.9 mmol) in THF (11 mL) was stirred for 16 hours at room temperature. The reaction mixture was concentrated in vacuo, diluted with EtOAc, and washed with saturated aqueous NH4Cl and brine. The organic layer was dried over MgSO4, filtered, and concentrated to give the crude material that was purified by silica gel flash column chromatography (100% hexanes to 1% to 2% EtOAc in hexanes) to afford the desired product (2.15 g, 79%).

Workup

  1. concentrationThe reaction mixture was concentrated in vacuo
  2. additiondiluted with EtOAc
  3. washwashed with saturated aqueous NH4Cl and brine
  4. dry with materialThe organic layer was dried over MgSO4
  5. filtrationfiltered
  6. concentrationconcentrated
  7. customto give the crude material that
  8. customwas purified by silica gel flash column chromatography (100% hexanes to 1% to 2% EtOAc in hexanes)

Sources & evidence

ORD record
ord-a9b26cc0fdfc4ec18e9feb4226bbfb3d
Source dataset
uspto-grants-2009_02
Patent number
US07485643B2

Reaction notes

Loading…