Methyl iodide → HCID 67812898, compound

HRID 2401441Notes

Reaction equation

HRID 2401441 reaction equation
[CH:1](NC(C)C)(C)C.[Li]CCCC.[CH3:13][C:14]1[S:23][C:22]2[C:21]3[C:24]([CH3:27])=[N:25][O:26][C:20]=3[C@H:19]([CH2:28][C:29]([O:31][C:32]([CH3:35])([CH3:34])[CH3:33])=[O:30])[NH:18][C:17](=[O:36])[C:16]=2[C:15]=1[CH3:37].IC>C1COCC1>[CH3:13][C:14]1[S:23][C:22]2[C:21]3[C:24]([CH3:27])=[N:25][O:26][C:20]=3[C@H:19]([C@@H:28]([CH3:1])[C:29]([O:31][C:32]([CH3:33])([CH3:34])[CH3:35])=[O:30])[NH:18][C:17](=[O:36])[C:16]=2[C:15]=1[CH3:37]

Participants

6

Reactant 4

HCID 6328Methyl iodideHCID 7912DiisopropylamineHCID 67813157HCID 67813157, compoundHCID 178418339Butyllithium

Product 1

HCID 67812898HCID 67812898, compoundYield 16.6%

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent

Conditions

Temperature
0 °C

Procedure

To a round bottomed flask was added THF (50 mL) and diisopropylamine (1.29 mL, 9.10 mmol) before the solution was cooled to 0° C. To this solution was added n-BuLi (3.62 mL, 8.69 mmol) and the reaction was stirred at 0° C. for 10 min before cooling to −78° C. and addition of tert-butyl 2-((6S)-2,3,9-trimethyl-4-oxo-5,6-dihydro-4H-isoxazolo[4,5-e]thieno[3,2-c]azepin-6-yl)acetate (1.5 g, 4.14 mmol), a form of intermediate 17, prepared according to Example 14. The solution was stirred at −78° C. for 1 h before addition of iodomethane (0.285 mL, 4.55 mmol) and warming to room temperature overnight. The reaction was quenched with saturated aqueous NH4Cl solution and then diluted with water and brine. The aqueous layer was extracted with EtOAc and the combined organic layer was dried over Na2SO4, filtered, and concentrated. The crude residue was purified via Biotage (MTBE/hexanes) to afford the titled product (0.259 g, 0.688 mmol).

Workup

  1. temperaturebefore cooling to −78° C.
  2. temperaturewarming to room temperature overnight
  3. customThe reaction was quenched with saturated aqueous NH4Cl solution
  4. additiondiluted with water and brine
  5. extractionThe aqueous layer was extracted with EtOAc
  6. dry with materialthe combined organic layer was dried over Na2SO4
  7. filtrationfiltered
  8. concentrationconcentrated
  9. customThe crude residue was purified via Biotage (MTBE/hexanes)

Sources & evidence

ORD record
ord-288ae664d2b04856a5d0696e78602cf3
Source dataset
uspto-grants-2014_08
Patent number
US08796261B2

Reaction notes

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