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

HRID 1847764Notes

Reaction equation

HRID 1847764 reaction equation
Br[C:2]1[CH:8]=[C:7]([N+:9]([O-:11])=[O:10])[CH:6]=[CH:5][C:3]=1[NH2:4].[CH3:12][C:13]([CH3:20])([C:18]#[CH:19])[C:14]([O:16][CH3:17])=[O:15].C(N(CC)CC)C>C1(C)C=CC=CC=1.O.[Cu]I.C1C=CC([P]([Pd]([P](C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)([P](C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)[P](C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)=CC=1>[NH2:4][C:3]1[CH:5]=[CH:6][C:7]([N+:9]([O-:11])=[O:10])=[CH:8][C:2]=1[C:19]#[C:18][C:13]([CH3:20])([CH3:12])[C:14]([O:16][CH3:17])=[O:15]

Participants

7

Reactant 3

HCID 8471TriethylamineHCID 25840Benzenamine, 2-bromo-4-nitro-HCID 15186997Methyl 2,2-dimethylbut-3-ynoate

Product 1

HCID 59129298Methyl 4-(2-amino-5-nitrophenyl)-2,2-dimethylbut-3-ynoateYield 9%

Reagents, catalysts & solvents 3

HCID 24350Copper(1+) iodide; Copper(I) iodide; Cuprous iodide; Cuprous iodide (CuI)CatalystHCID 178418397HCID 178418397, compoundCatalystHCID 22272177Toluene waterSolvent

Conditions

Temperature
70 °C

Procedure

To a deoxygenated solution of compound 2-bromo-4-nitroaniline (9.43 g, 43.7 mmol), methyl 2,2-dimethylbut-3-ynoate (5.00 g, 39.7 mmol), CuI (754 mg, 3.97 mmol) and triethylamine (8.03 g, 79.4 mmol) in toluene/H2O (100/30 mL) was added Pd(PPh3)4 (6.17 g, 3.97 mmol) under N2. The mixture was heated at 70° C. and stirred for 24 h. After cooling, the solid was filtered off and washed with EtOAc (50 mL×3). The organic layer was separated and the aqueous phase was washed with EtOAc (50 mL×3). The combined organic layers were dried and evaporated under reduced pressure to give a residue, which was purified by column chromatography on silica gel (petroleum ether/ethyl acetate=10/1) to obtain methyl 4-(2-amino-5-nitrophenyl)-2,2-dimethylbut-3-ynoate (900 mg, 9%). 1H NMR (400 MHz, CDCl3) δ 8.17 (d, J=2.8 Hz, 1H), 8.01 (dd, J=2.8, 9.2 Hz, 1H), 6.65 (d, J=9.2 Hz, 1H), 5.10 (brs, 2H), 3.80 (s, 3H), 1.60 (s, 6H).

Workup

  1. temperatureAfter cooling
  2. filtrationthe solid was filtered off
  3. washwashed with EtOAc (50 mL×3)
  4. customThe organic layer was separated
  5. washthe aqueous phase was washed with EtOAc (50 mL×3)
  6. customThe combined organic layers were dried
  7. customevaporated under reduced pressure
  8. customto give a residue, which
  9. customwas purified by column chromatography on silica gel (petroleum ether/ethyl acetate=10/1)

Sources & evidence

ORD record
ord-b02b05481c2044b49d83ed70439e0f49
Source dataset
uspto-grants-2015_02
Patent number
US08952049B2

Reaction notes

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