Diisopropylamine → Ethyl 2-(5,6,7,8-tetrahydroquinolin-2-yl)acetate

HRID 920891Notes

Reaction equation

HRID 920891 reaction equation
C(NC(C)C)(C)C.[Li]CCCC.CN(C)CCN(C)C.[CH3:21][C:22]1[CH:31]=[CH:30][C:29]2[CH2:28][CH2:27][CH2:26][CH2:25][C:24]=2[N:23]=1.[C:32](Cl)(=[O:36])[O:33][CH2:34][CH3:35].[Cl-].[NH4+]>O.C1COCC1>[N:23]1[C:24]2[CH2:25][CH2:26][CH2:27][CH2:28][C:29]=2[CH:30]=[CH:31][C:22]=1[CH2:21][C:32]([O:33][CH2:34][CH3:35])=[O:36]

Participants

9

Reactant 6

HCID 7912DiisopropylamineHCID 8037N,N,N',N'-TetramethylethylenediamineHCID 10928Ethyl chloroformateHCID 25517Ammonium ChlorideHCID 122294205,6,7,8-Tetrahydro-2-methylquinolineHCID 178418339Butyllithium

Product 1

HCID 86683110Ethyl 2-(5,6,7,8-tetrahydroquinolin-2-yl)acetateYield 29%

Reagents, catalysts & solvents 2

HCID 962WaterSolventHCID 8028TetrahydrofuranSolvent

Conditions

Temperature
-70 °C

Procedure

A solution of 7.56 g (74.7 mmol) of diisopropylamine in 100 mL of water-free THF was cooled to −30° C. and n-BuLi (31.9 g, 15% solution in n-hexane, 74.7 mmol mmol) was added via a syringe. The mixture was allowed to stir for 30 min. After cooling to −70° C., 8.68 g (74.7 mmol) tetramethylethylenediamine in 20 mL of THF were added and the mixture was allowed at −70° C. for 1 h. Then, 5 g (34.00 mmol) of 2-methyl-5,6,7,8-tetrahydroquinoline and 3.87 g (35.7 mmol) of ethyl carbonochloridate were added. The mixture was allowed to warm to room temperature within 2 h while being stirring. The reaction mixture was poured onto conc. cold aqueous ammonium chloride solution and extracted with EA (3 times). The combined organic phase was once extracted with a saturated ammonium chloride solution, washed with a saturated sodium bicarbonate solution and dried (magnesium sulfate). After removal of the solvent, the crude product was purified by flash column chromatography (eluent: heptane/EA 1/2) to provide 2.16 g (29%) of the title compound).

Workup

  1. waitthe mixture was allowed at −70° C. for 1 h
  2. temperatureto warm to room temperature within 2 h
  3. stirringwhile being stirring
  4. extractionextracted with EA (3 times)
  5. extractionThe combined organic phase was once extracted with a saturated ammonium chloride solution
  6. washwashed with a saturated sodium bicarbonate solution
  7. dry with materialdried (magnesium sulfate)
  8. customAfter removal of the solvent
  9. customthe crude product was purified by flash column chromatography (eluent: heptane/EA 1/2)

Sources & evidence

ORD record
ord-d87ad9e975f84c3c81b02406aeb16a6f
Source dataset
uspto-grants-2016_03
Patent number
US09273068B2

Reaction notes

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