tert-Butyl bromoacetate → [1-(4-Methoxy-benzyl)-2-oxo-1,2,3,4-tetrahydro-quinolin-3-yl]-acetic acid tert-butyl ester

HRID 851927Notes

Reaction equation

HRID 851927 reaction equation
[CH3:1][O:2][C:3]1[CH:20]=[CH:19][C:6]([CH2:7][N:8]2[C:17]3[C:12](=[CH:13][CH:14]=[CH:15][CH:16]=3)[CH2:11][CH2:10][C:9]2=[O:18])=[CH:5][CH:4]=1.[Li+].CC([N-]C(C)C)C.Br[CH2:30][C:31]([O:33][C:34]([CH3:37])([CH3:36])[CH3:35])=[O:32]>C1COCC1>[C:34]([O:33][C:31](=[O:32])[CH2:30][CH:10]1[CH2:11][C:12]2[C:17](=[CH:16][CH:15]=[CH:14][CH:13]=2)[N:8]([CH2:7][C:6]2[CH:5]=[CH:4][C:3]([O:2][CH3:1])=[CH:20][CH:19]=2)[C:9]1=[O:18])([CH3:37])([CH3:36])[CH3:35]

Participants

5

Reactant 3

HCID 79177tert-Butyl bromoacetateHCID 2724682Lithium diisopropylamideHCID 547654001-[(4-Methoxyphenyl)methyl]-3,4-dihydroquinolin-2(1H)-one

Product 1

HCID 69009889[1-(4-Methoxy-benzyl)-2-oxo-1,2,3,4-tetrahydro-quinolin-3-yl]-acetic acid tert-butyl esterYield 53%

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent3×

Conditions

Temperature
-78 °C

Procedure

The 1-(4-methoxy-benzyl)-3,4-dihydro-1H-quinolin-2-one (7.86 mmol) obtained in the previous step is dissolved in 10 mL of anhydrous THF. A solution of freshly prepared LDA (9.43 mmol) in 3.5 mL of anhydrous THF is added dropwise at −78° C. The reaction mixture is stirred at −78° C. for 10 minutes, warmed up to 0° C. for 15 minutes, and then cooled down to −78° C. again before it is transferred dropwise through a double-ended needle to a solution of tert-butyl bromoacetate (10.2 mmol) in 5 mL of anhydrous THF. The resultant solution is stirred at −78° C. for 1 hour before it is allowed to warm up to 0° C. within another hour and then quenched with MeOH. After removal of the solvent, the residue is purified by silica gel chromatography (hexane/EtOAc) to give [1-(4-methoxy-benzyl)-2-oxo-1,2,3,4-tetrahydro-quinolin-3-yl]-acetic acid tert-butyl ester as a light yellow oil. Yield: 53%. 1H NMR (400 MHz, CDCl3): δ 7.13 (m, 4H), 6.96 (t, 1H), 6.90 (d, 1H), 6.83 (d, 2H), 5.25 (d, 1H), 4.95 (d, 1H), 3.76 (s, 3H), 3.13 (m, 1H), 3.00-2.85 (m, 3H), 2.41 (dd, 1H), 1.48 (s, 9H). MS: (ES+): 404.2 [M+23].

Workup

  1. temperaturewarmed up to 0° C. for 15 minutes
  2. temperaturecooled down to −78° C. again before it
  3. temperatureto warm up to 0° C. within another hour
  4. customquenched with MeOH
  5. customAfter removal of the solvent
  6. customthe residue is purified by silica gel chromatography (hexane/EtOAc)

Sources & evidence

ORD record
ord-dbd518db22044451b679660c172b7557
Source dataset
uspto-grants-2007_08
Patent number
US07253164B2

Reaction notes

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