Toluene → HCID 21094005, compound

HRID 729703Notes

Reaction equation

HRID 729703 reaction equation
CN1C(=O)N(C)CCC1.[Li+].CC([N-]C(C)C)C.[CH3:18][S:19]([C:22]1[CH:27]=[CH:26][C:25]([CH2:28][C:29]([OH:31])=[O:30])=[CH:24][CH:23]=1)(=[O:21])=[O:20].Cl[CH2:33][C:34]1[S:35][CH:36]=[CH:37][CH:38]=1.C1(C)C=CC=CC=1>CCCCCCC.C1COCC1.C1(CC)C=CC=CC=1.C1COCC1>[CH3:18][S:19]([C:22]1[CH:23]=[CH:24][C:25]([CH:28]([CH2:33][C:34]2[S:35][CH:36]=[CH:37][CH:38]=2)[C:29]([OH:31])=[O:30])=[CH:26][CH:27]=1)(=[O:20])=[O:21]

Participants

8

Reactant 5

HCID 1140TolueneHCID 698302-(Chloromethyl)thiopheneHCID 816462(1H)-Pyrimidinone, tetrahydro-1,3-dimethyl-HCID 5723454-Mesylphenylacetic acidHCID 2724682Lithium diisopropylamide

Product 1

HCID 21094005HCID 21094005, compound

Reagents, catalysts & solvents 2

HCID 8028TetrahydrofuranSolvent4×HCID 22742125Tetrahydrofuran heptane ethylbenzolSolvent

Conditions

Temperature
20 °C

Procedure

DMPU (50 mL, 413 mmol) was added to a solution of LDA (65 mL of a 1.8M solution in n-C7H16-THF-PhEt, 117 mmol) in anhydrous THF (250 mL) at −78° C. The mixture was stirred for 1 h to generate a cream precipitate. A solution of (4-methanesulfonylphenyl)acetic acid (12.00 g, 56 mmol) in anhydrous THF (120 mL) was added over 20 min. More anhydrous THF (30 mL) was added, then the thick yellow slurry was stirred for 1 h. The mixture was treated with a solution of 2-chloromethylthiophene (7.50 g, 57 mmol) and PhMe (5.20 g, 57 mmol) in anhydrous THF (20 mL), then stirring was continued at −78° C. for 20 min. The reaction mixture was then allowed to warm to 20° C. over 16 h, before being quenched with H2O (500 mL). The THF was removed under reduced pressure, then 12M HCl was added to adjust the pH to 2. The mixture was extracted with EtOAc (2×300 mL), then the extracts were washed with H2O (2×200 mL) and brine (2×100 mL), before being dried (MgSO4). Filtration, solvent evaporation, and column chromatography (IH-EtOAc, 3:2 containing 0.5% AcOH) furnished the title compound: m/z (ES+)=638.3 [2M+NH4]+.

Workup

  1. stirringthe thick yellow slurry was stirred for 1 h
  2. stirringstirring
  3. waitwas continued at −78° C. for 20 min
  4. custombefore being quenched with H2O (500 mL)
  5. customThe THF was removed under reduced pressure
  6. addition12M HCl was added
  7. extractionThe mixture was extracted with EtOAc (2×300 mL)
  8. washthe extracts were washed with H2O (2×200 mL) and brine (2×100 mL)
  9. dry with materialbefore being dried (MgSO4)
  10. filtrationFiltration, solvent evaporation, and column chromatography (IH-EtOAc, 3:2 containing 0.5% AcOH)

Sources & evidence

ORD record
ord-e665df471a164326afa5699f34eca486
Source dataset
uspto-grants-2009_09
Patent number
US07582632B2

Reaction notes

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