Tetrahydrofuran → 4-(7-Chloro-2-oxazol-2-yl-4-oxo-1-phenyl-1,4-dihydro-quinolin-3-ylmethyl)-benzoic acid methyl ester

HRID 1261785Notes

Reaction equation

HRID 1261785 reaction equation
[Cl:1][C:2]1[CH:7]=[CH:6][C:5]([C:8](=[O:21])[CH2:9][CH2:10][C:11]2[CH:20]=[CH:19][C:14]([C:15]([O:17][CH3:18])=[O:16])=[CH:13][CH:12]=2)=[C:4]([NH:22][C:23]2[CH:28]=[CH:27][CH:26]=[CH:25][CH:24]=2)[CH:3]=1.C1COCC1.C[Si]([N-][Si](C)(C)C)(C)C.[Na+].[O:44]1[CH:48]=[CH:47][N:46]=[C:45]1[C:49](Cl)=O>CN(C=O)C>[CH3:18][O:17][C:15](=[O:16])[C:14]1[CH:19]=[CH:20][C:11]([CH2:10][C:9]2[C:8](=[O:21])[C:5]3[C:4](=[CH:3][C:2]([Cl:1])=[CH:7][CH:6]=3)[N:22]([C:23]3[CH:28]=[CH:27][CH:26]=[CH:25][CH:24]=3)[C:49]=2[C:45]2[O:44][CH:48]=[CH:47][N:46]=2)=[CH:12][CH:13]=1

Participants

6

Reactant 4

HCID 8028Tetrahydrofuran3×HCID 2724254Sodium bis(trimethylsilyl)amideHCID 22646749Oxazole-2-carbonyl chlorideHCID 70817153HCID 70817153, compound

Product 1

HCID 708169274-(7-Chloro-2-oxazol-2-yl-4-oxo-1-phenyl-1,4-dihydro-quinolin-3-ylmethyl)-benzoic acid methyl esterYield 2.6%

Reagents, catalysts & solvents 1

HCID 6228DimethylformamideSolvent

Procedure

Separately, in a 100 mL round-bottomed flask, methyl 4-(3-(4-chloro-2-(phenylamino)phenyl)-3-oxopropyl)benzoate (898 mg, 2.28 mmol) was combined with THF to give a yellow solution. A 1.0 M solution of NaHMDS in THF (5.7 ml, 5.7 mmol) was added. The reaction mixture was stirred at room temperature for 15 minutes. A heterogeneous mixture of oxazole-2-carbonyl chloride from above, THF (5 mL), DMF (500 μL) was added dropwise to the reaction mixture. The mixture was stirred at room temperature overnight. The reaction flask was cooled to 0° C., then the reaction was quenched with water. The resulting heterogeneous mixture was extracted with ethyl acetate, and the organic phase was dried over MgSO4, filtered, then concentrated. The crude product was dissolved in methylene chloride, then concentrated over silica gel. The silica gel supported crude product was loaded onto a 80 gram analogix column. Flash chromatography (15% EtOAc-hexanes→55% EtOAc-hexanes) provided 4-(7-Chloro-2-oxazol-2-yl-4-oxo-1-phenyl-1,4-dihydro-quinolin-3-ylmethyl)-benzoic acid methyl ester (28 mg, 2.6%) as a light yellow solid.

Workup

  1. customto give a yellow solution
  2. additionwas added dropwise to the reaction mixture
  3. stirringThe mixture was stirred at room temperature overnight
  4. temperatureThe reaction flask was cooled to 0° C.
  5. customthe reaction was quenched with water
  6. extractionThe resulting heterogeneous mixture was extracted with ethyl acetate
  7. dry with materialthe organic phase was dried over MgSO4
  8. filtrationfiltered
  9. concentrationconcentrated
  10. dissolutionThe crude product was dissolved in methylene chloride
  11. concentrationconcentrated over silica gel

Sources & evidence

ORD record
ord-91a85395c02c4e2e9faad6727c7d80db
Source dataset
uspto-grants-2013_06
Patent number
US08471027B2

Reaction notes

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