Ethyl bromoacetate → Ethyl 8-[1,1-dicarbomethoxy-2-carboethoxy-ethyl]-4-Oxo-4H-Quinolizine-3-Carboxylate

HRID 48913Notes

Reaction equation

HRID 48913 reaction equation
[H-].[Na+].C1COCC1.[C:8]([CH:12]([C:29]([O:31][CH3:32])=[O:30])[C:13]1[CH:14]=[CH:15][N:16]2[C:21]([CH:22]=1)=[CH:20][CH:19]=[C:18]([C:23]([O:25][CH2:26][CH3:27])=[O:24])[C:17]2=[O:28])([O:10][CH3:11])=[O:9].Br[CH2:34][C:35]([O:37][CH2:38][CH3:39])=[O:36]>O>[C:8]([C:12]([C:13]1[CH:14]=[CH:15][N:16]2[C:21]([CH:22]=1)=[CH:20][CH:19]=[C:18]([C:23]([O:25][CH2:26][CH3:27])=[O:24])[C:17]2=[O:28])([C:29]([O:31][CH3:32])=[O:30])[CH2:34][C:35]([O:37][CH2:38][CH3:39])=[O:36])([O:10][CH3:11])=[O:9]

Participants

6

Reactant 4

HCID 7748Ethyl bromoacetateHCID 8028TetrahydrofuranHCID 24758Sodium hydrideHCID 20634159Ethyl 8-(dicarbomethoxymethyl)-4-oxo-4H-quinolizine-3-carboxylate

Product 1

HCID 20634153Ethyl 8-[1,1-dicarbomethoxy-2-carboethoxy-ethyl]-4-Oxo-4H-Quinolizine-3-CarboxylateYield 74%

Reagents, catalysts & solvents 1

HCID 962WaterSolvent

Procedure

An oven-dried 50 ml three-necked round-bottom flask equipped with a reflux condenser was charged with NaH (160 mg, 60% suspension in oil, 4 mmol, washed with hexane) and 10 ml THF. Ethyl 8-(dicarbomethoxymethyl)-4-oxo-4H-quinolizine-3-carboxylate (19) (700 mg, 2 mmol) was added in three portions and stirring was continued for 1 h, followed by addition of ethyl bromoacetate (0.5 ml, 5.3 mmol). The reaction mixture was refluxed overnight, cooled to room temperature and poured into 100 ml water. The aqueous layer was extracted three times with 100 ml dichloromethane. The organic solvent was evaporated and the crude product was purified by flash chromatography (ethyl acetate) to give a yellow viscous oil (630 mg, 74%). 1H NMR (δ, CDCl3): 1.24 (t, J=7 Hz, 3H), 1.42 (t, J=7 Hz, 3H), 3.39 (s, 2H), 3.84 (s, 6H), 4.14 (q, J=7 Hz, 2H), 4.41 (q, J=7 Hz, 2H), 6.63 (d, J=8 Hz, 1H), 7.14 (dd, J=2 Hz, J=7 Hz, 1H), 7.61 (d, J=2 Hz, 1H), 8.40 (d, J=8 Hz, 1H), 9.29 (d, J=8 Hz, 1H). MS: m/z 433.1363; required for C21H21NO9: 433.1372.

Workup

  1. customAn oven-dried 50 ml three-necked round-bottom flask equipped with a reflux condenser
  2. temperatureThe reaction mixture was refluxed overnight
  3. extractionThe aqueous layer was extracted three times with 100 ml dichloromethane
  4. customThe organic solvent was evaporated
  5. customthe crude product was purified by flash chromatography (ethyl acetate)

Sources & evidence

ORD record
ord-7e8619840a5849f3b8f569399bdb912c
Source dataset
uspto-grants-2004_03
Patent number
US06706528B2

Reaction notes

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