Tetrahydrofuran → HCID 69451615, compound

HRID 2416188Notes

Reaction equation

HRID 2416188 reaction equation
COC(=O)C[C:5]1([C:10]2[CH:15]=[CH:14][N:13]=[CH:12][CH:11]=2)[NH:9][CH:8]=[CH:7][S:6]1.[Li+].C[Si]([N-][Si](C)(C)C)(C)C.[CH3:27][O:28][C:29](=[O:41])[C:30]1[CH:35]=[CH:34][CH:33]=[C:32]([N+:36]([O-])=O)[C:31]=1[CH2:39]Br.[NH4+].[Cl-].C1C[O:47][CH2:46][CH2:45]1>O.CCO.[Fe]>[CH3:27][O:28][C:29]([C:30]1[C:31]2[CH2:39][CH:45]([C:8]3[N:9]=[C:5]([C:10]4[CH:11]=[CH:12][N:13]=[CH:14][CH:15]=4)[S:6][CH:7]=3)[C:46](=[O:47])[NH:36][C:32]=2[CH:33]=[CH:34][CH:35]=1)=[O:41]

Participants

9

Reactant 5

HCID 8028Tetrahydrofuran2×HCID 25517Ammonium ChlorideHCID 1487795Methyl 2-(bromomethyl)-3-nitrobenzoateHCID 2733832Lithium HexamethyldisilazideHCID 86610487HCID 86610487, compound

Product 1

HCID 69451615HCID 69451615, compound

Reagents, catalysts & solvents 3

HCID 23925IronCatalystHCID 702EthanolSolventHCID 962WaterSolvent

Conditions

Temperature
-78 °C

Procedure

In an oven-dried, 25-mL, round-bottomed flask was placed 2-(4-pyridyl)-thiazole acetic acid methyl ester (Example 1a, 380 mg, 1.62 mmol) in THF (10 mL). The mixture was cooled to −78° C. and LHMDS (Aldrich, 1.0 M in THF, 1.62 mL) was added slowly. The reaction was stirred for 5 min, and the resulting enolate was added to a pre-cooled (−45° C.) solution of 2-bromomethyl-3-nitro-benzoic acid methyl ester in THF (10 mL) via a cannula over a period of 5 min. The reaction was stirred for additional 1.5 h, and quenched by saturated aq. NH4Cl (5 mL). The phases were separated, and the aqueous phase was extracted with EtOAc (50 mL). The combined organic layers were washed with brine (15 mL), dried over MgSO4, and concentrated in vacuo to afford the crude addition product. This material was employed in the next step without further purification. In a 50-mL, round-bottomed flask were placed the crude addition product, Fe powder (Aldrich, 454 mg, 8.0 mmol), and NH4Cl (70 mg, 1.3 mmol) in H2O (8 mL) and EtOH (8 mL). The mixture was heated at 80° C. for 12 h, and filtered while hot. The filtrate was concentrated in vacuo, and purified by flash chromatography (EtOAc) to afford 1,2,3,4-tetrahydro-2-oxo-3-[2-(4-pyridyl)-4-thiazolyl]-5-quinolinecarboxylic acid methyl ester as a yellow solid. Mp: 230-231° C. MS m/z: 366 (M+1). Calc'd for C19H15N3O3S: 365.08.

Workup

  1. stirringThe reaction was stirred for additional 1.5 h
  2. customquenched by saturated aq. NH4Cl (5 mL)
  3. customThe phases were separated
  4. extractionthe aqueous phase was extracted with EtOAc (50 mL)
  5. washThe combined organic layers were washed with brine (15 mL)
  6. dry with materialdried over MgSO4
  7. concentrationconcentrated in vacuo
  8. customto afford the crude
  9. additionaddition product
  10. customThis material was employed in the next step without further purification
  11. temperatureThe mixture was heated at 80° C. for 12 h
  12. filtrationfiltered while hot
  13. concentrationThe filtrate was concentrated in vacuo
  14. custompurified by flash chromatography (EtOAc)

Sources & evidence

ORD record
ord-4cdff08c051847e296ce17dbe3c2dd1e
Source dataset
uspto-grants-2004_11
Patent number
US06822097B1

Reaction notes

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