Methyl iodide → HCID 59621321, compound

HRID 1842138Notes

Reaction equation

HRID 1842138 reaction equation
[F:1][C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][C:3]=1[C@:8]12[CH2:17][C@H:16]([OH:18])[CH2:15][CH2:14][C@H:13]1[CH2:12][S:11][C:10]([N:19]([CH2:27][C:28]1[CH:33]=[CH:32][C:31]([O:34][CH3:35])=[CH:30][CH:29]=1)[C:20](=[O:26])[O:21][C:22]([CH3:25])([CH3:24])[CH3:23])=[N:9]2.CI.[H-].[Na+].[C:40](OCC)(=O)C>CN(C=O)C.O>[F:1][C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][C:3]=1[C@:8]12[CH2:17][C@H:16]([O:18][CH3:40])[CH2:15][CH2:14][C@H:13]1[CH2:12][S:11][C:10]([N:19]([CH2:27][C:28]1[CH:29]=[CH:30][C:31]([O:34][CH3:35])=[CH:32][CH:33]=1)[C:20](=[O:26])[O:21][C:22]([CH3:23])([CH3:24])[CH3:25])=[N:9]2

Participants

7

Reactant 4

HCID 6328Methyl iodide3×HCID 8857Ethyl AcetateHCID 24758Sodium hydride2×HCID 59621342HCID 59621342, compound

Product 1

HCID 59621321HCID 59621321, compound

Reagents, catalysts & solvents 2

HCID 962WaterSolventHCID 6228DimethylformamideSolvent

Procedure

tert-Butyl (±)-[(4aR*,7R*,8aS*)-8a-(2-fluorophenyl)-7-hydroxy-4a,5,6,7,8,8a-hexahydro-4H-benzo[d][1,3]thiazin-2-yl]-(4-methoxybenzyl)carbamate obtained in Preparation Example 58-(9) (541 mg) was dissolved in DMF (5 mL). Methyl iodide (113 μL, specific gravity: 2.28 g/cm3) was added and then the mixture was cooled in an ice bath under a nitrogen atmosphere. Sodium hydride (60%, 55 mg) was added, followed by stirring for one hour and 45 minutes. Thereafter, methyl iodide (113 μL, specific gravity: 2.28 g/cm3) and sodium hydride (60%, 55 mg) were added, and the mixture was warmed to room temperature and stirred for one hour and 45 minutes. Thereafter, methyl iodide (113 μL, specific gravity: 2.28 g/cm3) was further added, followed by stirring for 13 hours. Ethyl acetate and water were added to the reaction solution, followed by further stirring. Then, the aqueous layer was separated. The organic layer was sequentially washed with a saturated ammonium chloride solution, water and brine. The resulting organic layer was dried over anhydrous magnesium sulfate, and the solid was removed by filtration. The filtrate was concentrated under reduced pressure and then purified by silica gel column chromatography to obtain the title compound (409 mg).

Workup

  1. temperaturethe mixture was cooled in an ice bath under a nitrogen atmosphere
  2. stirringstirred for one hour and 45 minutes
  3. stirringby stirring for 13 hours
  4. customThen, the aqueous layer was separated
  5. washThe organic layer was sequentially washed with a saturated ammonium chloride solution, water and brine
  6. dry with materialThe resulting organic layer was dried over anhydrous magnesium sulfate
  7. customthe solid was removed by filtration
  8. concentrationThe filtrate was concentrated under reduced pressure
  9. custompurified by silica gel column chromatography

Sources & evidence

ORD record
ord-18324054b8f940de8b358581a5a4b18e
Source dataset
uspto-grants-2015_02
Patent number
US08946211B2

Reaction notes

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