Diisopropylamine → Methyl 2-(2-fluorophenylamino)-3,4-difluoro-5-((trimethylsilyl)ethynyl)benzoate

HRID 558244Notes

Reaction equation

HRID 558244 reaction equation
Br[C:2]1[C:3]([F:21])=[C:4]([F:20])[C:5]([NH:12][C:13]2[CH:18]=[CH:17][CH:16]=[CH:15][C:14]=2[F:19])=[C:6]([CH:11]=1)[C:7]([O:9][CH3:10])=[O:8].N(C(C)C)C(C)C.[Si:29]([C:33]#[CH:34])([CH3:32])([CH3:31])[CH3:30]>C1COCC1.[Cu]I.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>[F:19][C:14]1[CH:15]=[CH:16][CH:17]=[CH:18][C:13]=1[NH:12][C:5]1[C:4]([F:20])=[C:3]([F:21])[C:2]([C:34]#[C:33][Si:29]([CH3:32])([CH3:31])[CH3:30])=[CH:11][C:6]=1[C:7]([O:9][CH3:10])=[O:8]

Participants

7

Reactant 3

HCID 7912DiisopropylamineHCID 66111TrimethylsilylacetyleneHCID 59519391Methyl 5-bromo-2-(2-fluorophenylamino)-3,4-difluorobenzoate

Product 1

HCID 59519400Methyl 2-(2-fluorophenylamino)-3,4-difluoro-5-((trimethylsilyl)ethynyl)benzoateYield 85.1%

Reagents, catalysts & solvents 3

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

Procedure

To an oven dried flask charged with a solution of methyl 5-bromo-2-(2-fluorophenylamino)-3,4-difluorobenzoate (21.68 mmol, 8.1 g) in THF (116 ml), was added CuI (2.16 mmol, 0.4 g) and iPr2NH (43.36 mmol, 6.1 ml). After addition is completed, reaction was purged with Argon and Pd(PPh3)2Cl2 (3.73 mmol, 2.62 g) and TMS-acetylene (26.88 mmol, 3.7 ml) are added. The reaction mixture was stirred at room temperature for 16 h, concentrated and taken up in EtOAc. The organic fraction was washed with sat NH4Cl, brine, dried over MgSO4 and conc. The crude was purified by flash chromatography using 5% to 20% EtOAc in Hexane to afford the desired product 6.96 g (85%).

Workup

  1. customTo an oven dried flask
  2. additionAfter addition
  3. customreaction
  4. additionare added
  5. concentrationconcentrated
  6. washThe organic fraction was washed with sat NH4Cl, brine
  7. dry with materialdried over MgSO4
  8. customconc. The crude was purified by flash chromatography

Sources & evidence

ORD record
ord-38d7f5ff75a74078a3ceb1ab52de9449
Source dataset
uspto-grants-2011_11
Patent number
US08063049B2

Reaction notes

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