Ethyl Acetate → HCID 59621342, compound

HRID 1842250Notes

Reaction equation

HRID 1842250 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]([NH:19][C:20](=[O:26])[O:21][C:22]([CH3:25])([CH3:24])[CH3:23])=[N:9]2.[CH3:27][O:28][C:29]1[CH:36]=[CH:35][C:32]([CH2:33]Cl)=[CH:31][CH:30]=1.C(=O)([O-])[O-].[K+].[K+].C(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]([OH:18])[CH2:15][CH2:14][C@H:13]1[CH2:12][S:11][C:10]([N:19]([CH2:33][C:32]1[CH:35]=[CH:36][C:29]([O:28][CH3:27])=[CH:30][CH:31]=1)[C:20](=[O:26])[O:21][C:22]([CH3:23])([CH3:25])[CH3:24])=[N:9]2

Participants

7

Reactant 4

HCID 8857Ethyl AcetateHCID 11430Potassium CarbonateHCID 699934-Methyloxybenzyl chlorideHCID 67478087HCID 67478087, compound

Product 1

HCID 59621342HCID 59621342, 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]carbamate obtained in Preparation Example 58-(8) (500 mg) was dissolved in DMF (10 mL), and the mixture was cooled in an ice bath under a nitrogen atmosphere. p-Methoxybenzyl chloride (161 μL, specific gravity: 1.154 g/cm3) and potassium carbonate (247 mg) were added thereto, followed by stirring for one hour. Thereafter, the reaction solution was warmed to room temperature and stirred for 19 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 (541 mg).

Workup

  1. temperaturethe mixture was cooled in an ice bath under a nitrogen atmosphere
  2. stirringstirred for 19 hours
  3. customThen, the aqueous layer was separated
  4. washThe organic layer was sequentially washed with a saturated ammonium chloride solution, water and brine
  5. dry with materialThe resulting organic layer was dried over anhydrous magnesium sulfate
  6. customthe solid was removed by filtration
  7. concentrationThe filtrate was concentrated under reduced pressure
  8. custompurified by silica gel column chromatography

Sources & evidence

ORD record
ord-a78eca924e8c4d00a17f6c70fe2f0be9
Source dataset
uspto-grants-2015_02
Patent number
US08946210B2

Reaction notes

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