Dimethylformamide → Ethyl 8-(4-Methoxyphenyl)-4-Oxo-4H-Quinolizine-3-Carboxylate

HRID 48914

Reaction equation

HRID 48914 reaction equation
Cl[C:2]1[CH:3]=[CH:4][N:5]2[C:10]([CH:11]=1)=[CH:9][CH:8]=[C:7]([C:12]([O:14][CH2:15][CH3:16])=[O:13])[C:6]2=[O:17].[CH3:18][O:19][C:20]1[CH:25]=[CH:24][C:23](B(O)O)=[CH:22][CH:21]=1.[F-].[Cs+].CN(C=O)C>O.C(OCC)(=O)C>[CH3:18][O:19][C:20]1[CH:25]=[CH:24][C:23]([C:2]2[CH:3]=[CH:4][N:5]3[C:10]([CH:11]=2)=[CH:9][CH:8]=[C:7]([C:12]([O:14][CH2:15][CH3:16])=[O:13])[C:6]3=[O:17])=[CH:22][CH:21]=1

Participants

7

Reactant 4

HCID 6228DimethylformamideHCID 25953Cesium fluorideHCID 201262(4-Methoxyphenyl)boronic acidHCID 3314858Ethyl 8-chloro-4-oxo-4H-quinolizine-3-carboxylate

Product 1

HCID 20634155Ethyl 8-(4-Methoxyphenyl)-4-Oxo-4H-Quinolizine-3-CarboxylateYield 52.6%

Reagents, catalysts & solvents 2

HCID 962WaterSolventHCID 8857Ethyl AcetateSolvent

Conditions

Temperature
110 °C

Procedure

An oven-dried 50 ml round-bottom flask equipped with reflux condenser was purged with argon, followed by addition of ethyl 8-chloro-4-oxo-4H-quinolizine-3-carboxylate (2) (500 mg, 2 mmol), 4-methoxyphenylboronic acid (372 mg, 2.4 mmol), CsF (600 mg, 3.9 mmol), PdCl2[P(c-Hex)3]2 (80 mg, 0.1 mmol) and 6 ml DMF. The reaction mixture was stirred at 110° C. for 12 h and cooled to room temperature. Completion of the reaction was indicated by thin layer chromatography (ethyl acetate). The reaction mixture was poured into 100 ml water and extracted three times with 100 ml chloroform. The combined organic layers were washed three times with 50 ml water. The organic solvent was evaporated and the crude product was further purified by column chromatography (5% MeOH in ethyl acetate) to give a bright yellow solid (340 mg, 50% yield). M.p. 205-209° C. 1H NMR (δ, CDCl3): 1.43 (t, J=7 Hz, 3H), 3.90 (s, 3H), 4.42 (q, J=7 H, 2H), 6.65 (d, J=8 Hz, 1H), 7.05 (d, J=9 Hz, 2H), 7.43 (dd, J=2 Hz, J=7 Hz, 1H), 7.58-7.80 (m, 3H), 8.37 (d, J=8 Hz, 1H), 9.41 (d, J=7 Hz, 1H). MS: m/z 323.1159; required for C19H17NO4: 323.1157.

Workup

  1. customAn oven-dried 50 ml round-bottom flask equipped
  2. temperaturewith reflux condenser
  3. customwas purged with argon
  4. temperaturecooled to room temperature
  5. extractionextracted three times with 100 ml chloroform
  6. washThe combined organic layers were washed three times with 50 ml water
  7. customThe organic solvent was evaporated
  8. customthe crude product was further purified by column chromatography (5% MeOH in ethyl acetate)

Sources & evidence

ORD record
ord-e4fec1a4088f49eaaccdd469502b69ad
Source dataset
uspto-grants-2004_03
Patent number
US06706528B2

Linked notes

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