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

HRID 917012Notes

Reaction equation

HRID 917012 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 77%

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 (4) (101 mg, 0.268 mmol), TMS-acetylene (0.045 mL, 0.31 mmol), Pd(PPh3)2Cl2 (18.7 mg, 0.0261 mmol), CuI (5.1 mg, 0.027 mmol), and i-Pr2NH (0.075 mL, 0.53 mmol) in THF (1.5 mL) was stirred for 16 hours at room temperature. The reaction mixture was concentrated under reduced pressure, and diluted with EtOAc. The organic layer was washed with saturated aqueous NH4Cl and brine, dried over MgSO4, and concentrated. Purification by flash column chromatography using the Biotage system (100% hexane to 1% EtOAc in hexane) gave 81.3 mg (77% yield) of the desired product (5).

Workup

  1. concentrationThe reaction mixture was concentrated under reduced pressure
  2. additiondiluted with EtOAc
  3. washThe organic layer was washed with saturated aqueous NH4Cl and brine
  4. dry with materialdried over MgSO4
  5. concentrationconcentrated
  6. customPurification by flash column chromatography

Sources & evidence

ORD record
ord-f2abaae3933c4655b6c3af0b2762405b
Source dataset
uspto-grants-2007_09
Patent number
US07271178B2

Reaction notes

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