Trifluoroacetic acid → HCID 67441977, compound

HRID 1801349Notes

Reaction equation

HRID 1801349 reaction equation
O[CH:2]1[C:11]2[C:6](=[CH:7][CH:8]=[C:9]([C:12]([O:14][CH3:15])=[O:13])[CH:10]=2)[NH:5][CH:4]([C:16]2[CH:21]=[CH:20][CH:19]=[CH:18][C:17]=2[N+:22]([O-])=O)[C:3]1([CH3:26])[CH3:25].C([SiH](CC)CC)C.FC(F)(F)C(O)=O>ClCCl>[NH2:22][C:17]1[CH:18]=[CH:19][CH:20]=[CH:21][C:16]=1[CH:4]1[C:3]([CH3:25])([CH3:26])[CH2:2][C:11]2[C:6](=[CH:7][CH:8]=[C:9]([C:12]([O:14][CH3:15])=[O:13])[CH:10]=2)[NH:5]1

Participants

5

Reactant 3

HCID 6422Trifluoroacetic acidHCID 12052TriethylsilaneHCID 67440987HCID 67440987, compound

Product 1

HCID 67441977HCID 67441977, compoundYield 96.7%

Reagents, catalysts & solvents 1

HCID 6344DichloromethaneSolvent2×

Procedure

To a mixture of (E)-methyl 4-(2-nitrobenzylideneamino) benzoate (3.26 g, 11.5 mmol) and yttrium(III) trifluoromethanesulfonate (140 mg, 0.27 mmol) in tetrahydrofuran (28 mL) was added isobutylaldehyde (1.9 mL, 20.6 mmol) at room temperature under nitrogen, then the resultant mixture was stirred at room temperature overnight. Thin layer chromatography and LC-MS showed the starting material was completely consumed. The reaction was quenched with water and separated. The aqueous layer was extracted with ethyl acetate twice and the combined organic layers were concentrated in vacuo. The residue was purified by column chromatography (petroleum ether/ethyl acetate=3:1) to afford 1.34 g of methyl 4-hydroxy-3,3-dimethyl-2-(2-nitrophenyl)-1,2,3,4-tetrahydroquinoline-6-carboxylate as a yellow solid. Yield: 32.7%. To an ice-cooled mixture of methyl 4-hydroxy-3,3-dimethyl-2-(2-nitrophenyl)-1,2,3,4-tetrahydroquinoline-6-carboxylate (1.5 g, 4.2 mmol) and triethylsilane (1.48 g, 12.6 mmol) in dichloro methane (150 mL) was added dropwise a solution of trifluoroacetic acid (1.92 g, 16.8 mmol) in dichloromethane (50 mL) over 45 min under nitrogen. The mixture was kept at 0° C. at room temperature for 12 h. Thin layer chromatography and LC-MS showed the starting material was completely consumed. Solid sodium carbonate (2.0 g) was added to the reaction mixture and stirred for 10 min., filtered. The filtrate was concentrated and purified by column chromatography (petroleum ether/ethyl acetate=3:1) to afford 1.26 g of methyl 2-(2-aminophenyl)-3,3-dimethyl-1,2,3,4-tetrahydroquinoline-6-carboxylate as a yellow solid. Yield: 86%.

Workup

  1. customwas completely consumed
  2. additionSolid sodium carbonate (2.0 g) was added to the reaction mixture
  3. filtrationfiltered
  4. concentrationThe filtrate was concentrated
  5. custompurified by column chromatography (petroleum ether/ethyl acetate=3:1)

Sources & evidence

ORD record
ord-cca203be9cea47a6811ae06ed420a974
Source dataset
uspto-grants-2013_01
Patent number
US08344137B2

Reaction notes

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