Aniline → N-(2-Methylbut-3-yn-2-yl)aniline

HRID 1939585Notes

Reaction equation

HRID 1939585 reaction equation
[NH2:1][C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][CH:3]=1.C(O[C:12]([CH3:16])([CH3:15])[C:13]#[CH:14])(=O)C.CCN(CC)CC>C1COCC1.Cl[Cu]>[CH3:15][C:12]([NH:1][C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][CH:3]=1)([CH3:16])[C:13]#[CH:14]

Participants

6

Reactant 3

HCID 6115AnilineHCID 8471TriethylamineHCID 741441,1-Dimethylprop-2-ynyl acetate

Product 1

HCID 345768N-(2-Methylbut-3-yn-2-yl)anilineYield 67%

Reagents, catalysts & solvents 2

HCID 62652Cuprous chlorideCatalystHCID 8028TetrahydrofuranSolvent

Procedure

A solution of aniline (19 mL, 0.20 mol), 3-acetoxy-3-methyl-1-butyne (26 g, 0.20 mol), CuCl (1.0 g, 10 mmol) and Et3N (28 mL, 0.20 mol) in THF (120 mL) was heated at reflux for 5 h and was filtered through a pad of Celite™. Removal of solvent and chromatography of the crude mixture (silica gel, EtOAc/hexane, 3/7 ) afforded 21 g (67%) of 3-methyl-3-phenylamino-1-butyne. Treatment of the aminobutyne with CuCl (0.70 mg, 7.0 mmol) in THF (200 mL ) at 70° C. for 16 h followed by chromatography (silica gel, EtOAc/hexane, 3/7) afforded 13 g (60%) of 1,2-dihydro-2,2-dimethylquinoline (structure 75A of Scheme LII, where R1 =H, R2-3 =methyl). Treatment of the quinoline with di-tert-butyl dicarbonate (22 g, 0.10 mol) and DMAP (12 g, 0.10 mol) in THF (100 mL ) for 16 h followed by chromatography (silica gel, EtOAc/hexane, 2/8) afforded 15 g (71%) of 1-tert-butoxycarbonyl-1,2-dihydro-2,2-dimethylquinoline. 1-tert-Butoxycarbonyl-1,2-dihydro-2,2-dimethylquinoline (3.0 g, 11 mmol) in THF (30 mL ) was treated with 1.0M BH3 -THF in THF (29 mL, 29 mmol) at rt for 3 h and was quenched with 3M KOH (20 mL). To the above solution 30% H2O2 (5 mL) was added and the mixture was stirred for 60 min, then 5 mL of water was introduced. The mixture was extracted, washed with brine and concentrated. Chromatography of the crude mixture on a silica gel column using a 10-30% mixture of EtOAc/Hexane as eluents afforded a 2:1 mixture of two isomers (0.87 g, 3.1 mmol), which was oxidized with PCC (2.5 g, 11 mmol) in 60 mL of methylene chloride at rt for 60 min. Removal of solvent and chromatography of the black oil on a silica gel column using a 20% mixture of EtOAc and hexane as solvent afforded 0.58 g (68%) of 1-tert-butoxycarbonyl-1,2,3,4-tetrahydro-2,2-dimethyl-4-quinolinone as a white solid. Data for 1-tert-butoxycarbonyl-1,2,3,4-tetrahydro-2,2-dimethyl-4-quinolinone: 1H NMR (400 MHz, CDCl3) 7.93 (d, J=7.8, 1H), 7.42 (t, J=7.8, 1H), 7.31 (d, J=7.8, 1H), 7.02 (t, J=7.8, 1H), 2.73 (s, 2H), 1.56 (s, 9H), 1.49 (s, 6H).

Workup

  1. temperatureat reflux for 5 h
  2. filtrationwas filtered through a pad of Celite™
  3. customRemoval of solvent and chromatography of the crude mixture (silica gel, EtOAc/hexane, 3/7 )

Sources & evidence

ORD record
ord-0cd2effb218d41cea65c870ca3cbd388
Source dataset
uspto-grants-1997_12
Patent number
US05696133

Reaction notes

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