Methyl chloroformate → HCID 58790151, compound

HRID 418717Notes

Reaction equation

HRID 418717 reaction equation
[N:1]1[CH:6]=[CH:5][CH:4]=[C:3]([N:7]2[CH2:11][CH2:10][CH2:9][C:8]2=[O:12])[CH:2]=1.[Li+].CC([N-]C(C)C)C.Cl[C:22]([O:24][CH3:25])=[O:23]>C1COCC1>[O:12]=[C:8]1[CH:9]([C:22]([O:24][CH3:25])=[O:23])[CH2:10][CH2:11][N:7]1[C:3]1[CH:2]=[N:1][CH:6]=[CH:5][CH:4]=1

Participants

5

Reactant 3

HCID 6586Methyl chloroformateHCID 2724682Lithium diisopropylamideHCID 58790312HCID 58790312, compound

Product 1

HCID 58790151HCID 58790151, compoundYield 26%

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent

Procedure

To a stirred solution of 349 (1.48 g, 9.1 mmol) in anhydrous THF (25 ml) at −78° C. under nitrogen was slowly added a solution of LDA (mono THF, 13.4 mL, 20.1 mmol, 1.5 M in cyclohexane). After 45 min, methyl chloroformate (776 μL, 10.0 mmol) was added. The mixture was warmed to room temperature over 2 h, and then stirred overnight. Then, the reaction mixture was quenched by addition of sat. ammonium chloride and extracted with AcOEt. After separation, the organic layer was successively washed with sat. NH4Cl, water, and brine. The aqueous phase was extracted twice with AcOEt. The combined organic layers were dried over anhydrous magnesium sulfate, filtered, and concentrated. The crude product was purified by flash column chromatography (eluents MeOH/CH2Cl2: 2/98 to 5/95) to afford title compound 350 (520 mg, 26% yield) as a pale yellow sticky solid. 1H NMR (400 MHz, DMSO-d6) δ (ppm): 8.86 (d, J=2.5 Hz, 1H), 8.38 (dd, J=4.7, 1.4 Hz, 1H), 8.12-8.06 (m, 1H), 7.44 (dd, J=8.4, 4.7 Hz, 1H), 3.99-3.84 (m, 2H), 3.81 (t, J=8.8 Hz, 1H), 3.70 (s, 3H), 2.48-2.29 (m, 2H). MS (m/z): 221.0 (M+H)+−.

Workup

  1. customThen, the reaction mixture was quenched by addition of sat. ammonium chloride
  2. extractionextracted with AcOEt
  3. customAfter separation
  4. washthe organic layer was successively washed with sat. NH4Cl, water, and brine
  5. extractionThe aqueous phase was extracted twice with AcOEt
  6. dry with materialThe combined organic layers were dried over anhydrous magnesium sulfate
  7. filtrationfiltered
  8. concentrationconcentrated
  9. customThe crude product was purified by flash column chromatography (eluents MeOH/CH2Cl2: 2/98 to 5/95)

Sources & evidence

ORD record
ord-4df11887755c4acab412d649a3911187
Source dataset
uspto-grants-2012_01
Patent number
US08093264B2

Reaction notes

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