Triethylamine → Benzyl 4-(2-amino-4-fluoro-5-nitrophenyl)-2,2-dimethylbut-3-ynoate

HRID 468519Notes

Reaction equation

HRID 468519 reaction equation
Br[C:2]1[CH:8]=[C:7]([N+:9]([O-:11])=[O:10])[C:6]([F:12])=[CH:5][C:3]=1[NH2:4].C[C:14]([CH3:27])([C:25]#[CH:26])[C:15]([O:17][C:18](=[O:24])[C:19]([CH3:23])([CH3:22])[C:20]#[CH:21])=O.[CH3:28][CH2:29]N(CC)CC>[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>[NH2:4][C:3]1[CH:5]=[C:6]([F:12])[C:7]([N+:9]([O-:11])=[O:10])=[CH:8][C:2]=1[C:21]#[C:20][C:19]([CH3:22])([CH3:23])[C:18]([O:17][CH2:15][C:14]1[CH:25]=[CH:26][CH:29]=[CH:28][CH:27]=1)=[O:24]

Participants

6

Reactant 3

HCID 8471TriethylamineHCID 574885132-Bromo-5-fluoro-4-nitroanilineHCID 866304972,2-Dimethylbut-3-ynoic anhydride

Product 1

HCID 59129571Benzyl 4-(2-amino-4-fluoro-5-nitrophenyl)-2,2-dimethylbut-3-ynoateYield 56%

Reagents, catalysts & solvents 2

HCID 24350Copper(1+) iodide; Copper(I) iodide; Cuprous iodide; Cuprous iodide (CuI)CatalystHCID 178418476HCID 178418476, compoundCatalyst

Conditions

Temperature
80 °C

Procedure

To a solution of 2-bromo-5-fluoro-4-nitroaniline (23.0 g, 0.1 mol) in Et3N (250 mL) was added benzoic 2,2-dimethylbut-3-ynoic anhydride (59.0 g, 0.29 mol), CuI (1.85 g) and Pd(PPh3)2Cl2 (2.3 g) at room temperature. The mixture was stirred at 80° C. overnight, After cooling to room temperature, the reaction was quenched with water and the aqueous layer was extracted with ethyl acetate (100 mL×3). The combined organic layer was dried over anhydrous Na2SO4, the solvent was evaporated in vacuo. The residue was purified by chromatography on silica gel (10% ethyl acetate in petroleum ether) to give benzyl 4-(2-amino-4-fluoro-5-nitrophenyl)-2,2-dimethylbut-3-ynoate (20.0 g, 56%). 1H NMR (400 MHz, CDCl3) 8.05 (d, J=8.4 Hz, 1H), 7.39-7.38 (m, 5H), 6.33 (d, J=13.2 Hz, 1H), 5.20 (s, 2H), 4.89 (br s, 2H), 1.61 (s, 6H).

Workup

  1. temperatureAfter cooling to room temperature
  2. customthe reaction was quenched with water
  3. extractionthe aqueous layer was extracted with ethyl acetate (100 mL×3)
  4. dry with materialThe combined organic layer was dried over anhydrous Na2SO4
  5. customthe solvent was evaporated in vacuo
  6. customThe residue was purified by chromatography on silica gel (10% ethyl acetate in petroleum ether)

Sources & evidence

ORD record
ord-eb652fa9f4e24b03a63cb7946e1d24ca
Source dataset
uspto-grants-2014_01
Patent number
US08623905B2

Reaction notes

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