Diisopropylamine → 2-(2-Chlorophenylamino)-3,4-difluoro-5-trimethylsilanylethynylbenzoic acid methyl ester

HRID 500565Notes

Reaction equation

HRID 500565 reaction equation
[CH3:1][O:2][C:3](=[O:21])[C:4]1[CH:9]=[C:8](Br)[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[CH:9]=[C:8]([C:27]#[C:26][Si:22]([CH3:25])([CH3:24])[CH3:23])[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 865967715-Bromo-2-(2-chlorophenylamino)-3,4-difluorobenzoic acid methyl ester

Product 1

HCID 865967722-(2-Chlorophenylamino)-3,4-difluoro-5-trimethylsilanylethynylbenzoic acid methyl esterYield 85%

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 5-bromo-2-(2-chlorophenylamino)-3,4-difluorobenzoic acid methyl ester (8.02 g, 21.3 mmol, prepared as described in Example 1), TMS-acetylene (3.80 mL, 26.4 mmol), Pd(PPh3)2Cl2 (1.52 g, 2.12 mmol), CuI (405 mg, 2.12 mmol), and i-Pr2NH (6.00 mL, 42.6 mmol) in THF (120 mL) was stirred for 3 days 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, and filtered. The organic layer was concentrated to give the crude material which was purified by silica gel flash column chromatography (100% Hexane to 1% to 2% EtOAc in Hexane) to afford the desired product (7.11 g, 85%).

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. concentrationThe organic layer was concentrated
  7. customto give the crude material which
  8. customwas purified by silica gel flash column chromatography (100% Hexane to 1% to 2% EtOAc in Hexane)

Sources & evidence

ORD record
ord-d6dc85bcf4014a01b8cd1ad1f42ffe51
Source dataset
uspto-grants-2010_08
Patent number
US07772234B2

Reaction notes

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