Hydrochloric Acid → HCID 58495302, compound

HRID 516254Notes

Reaction equation

HRID 516254 reaction equation
[Br:1][C:2]1[C:17]([OH:18])=[CH:16][C:5]2[CH2:6][CH2:7][N:8]([C:11]([O:13][CH2:14][CH3:15])=[O:12])[CH2:9][CH2:10][C:4]=2[CH:3]=1.[H-].[Na+].[CH3:21][C@@H:22]1[CH2:26]OS(=O)(=O)[N:23]1C(OC(C)(C)C)=O.Cl>CN(C=O)C.O>[NH2:23][C@H:22]([CH3:26])[CH2:21][O:18][C:17]1[C:2]([Br:1])=[CH:3][C:4]2[CH2:10][CH2:9][N:8]([C:11]([O:13][CH2:14][CH3:15])=[O:12])[CH2:7][CH2:6][C:5]=2[CH:16]=1

Participants

7

Reactant 4

HCID 313Hydrochloric AcidHCID 24758Sodium hydrideHCID 46172873(4R)-2,2-Dioxido-4-methyl-1,2,3-oxathiazolidine,N-BOC protectedHCID 58495428HCID 58495428, compound

Product 1

HCID 58495302HCID 58495302, compoundYield 112.5%

Reagents, catalysts & solvents 2

HCID 962WaterSolventHCID 6228DimethylformamideSolvent

Procedure

Under an argon atmosphere, to a solution of 1.7 g of ethyl 7-bromo-8-hydroxy-1,2,4,5-tetrahydro-3H-3-benzazepine-3-carboxylate in 30 ml of DMF was added 283 mg of sodium hydride under ice-cooling, followed by stirring at the same temperature for 10 minutes. Then, 1.54 g of t-butyl (4R)-4-methyl-2,2-dioxo-[1,2,3]oxathiazolidine-3-carboxylate was added thereto, followed by stirring at room temperature for 18 hours. To the reaction mixture was added water and 1 M aqueous hydrochloric acid sequentially, followed by stirring, and the precipitated solid was collected by filtration. To 20 ml of a suspension of the resulting solid in ethanol was added 10 ml of a 4 M hydrogen chloride-ethyl acetate solution under ice-cooling, followed by stirring at 60° C. for 1 hour. The reaction mixture was evaporated under reduced pressure, and to the residue were added chloroform and saturated aqueous sodium bicarbonate. After extraction with chloroform, the combined organic layer was washed with saturated brine, dried over anhydrous magnesium sulfate, filtered, and concentrated under reduced pressure to obtain 2.26 g of ethyl 7-{[(2R)-2-aminopropyl]oxy}-8-bromo-1,2,4,5-tetrahydro-3H-3-benzazepine-3-carboxylate as an opaque cream-colored oily substance.

Workup

  1. temperaturecooling
  2. stirringby stirring at room temperature for 18 hours
  3. stirringby stirring
  4. filtrationthe precipitated solid was collected by filtration
  5. additionTo 20 ml of a suspension of the resulting solid in ethanol was added 10 ml of a 4 M hydrogen chloride-ethyl acetate solution under ice-
  6. temperaturecooling
  7. stirringby stirring at 60° C. for 1 hour
  8. customThe reaction mixture was evaporated under reduced pressure
  9. additionto the residue were added chloroform and saturated aqueous sodium bicarbonate
  10. extractionAfter extraction with chloroform
  11. washthe combined organic layer was washed with saturated brine
  12. dry with materialdried over anhydrous magnesium sulfate
  13. filtrationfiltered
  14. concentrationconcentrated under reduced pressure

Sources & evidence

ORD record
ord-5dcd7f408745452bb0d2eaba1774b65a
Source dataset
uspto-grants-2015_08
Patent number
US09108977B2

Reaction notes

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