Hydrochloric Acid → HCID 68577108, compound

HRID 2390912Notes

Reaction equation

HRID 2390912 reaction equation
[ClH:1].O[CH2:3][CH2:4][N:5]([CH2:15][C:16]1[CH:21]=[CH:20][CH:19]=[CH:18][CH:17]=1)[CH2:6][C@@H:7]([C:9]1[CH:14]=[CH:13][CH:12]=[CH:11][CH:10]=1)O.[OH-].[Na+].C(N(CC)CC)C.CS([Cl:35])(=O)=O.[CH2:36]([NH2:39])[CH:37]=[CH2:38].C(=O)([O-])[O-].[Na+].[Na+].Cl.C(O)(C)C>C(OCC)(=O)C.C1(C)C=CC=CC=1.O>[ClH:35].[ClH:1].[C:9]1([C@@H:7]2[CH2:6][N:5]([CH2:15][C:16]3[CH:21]=[CH:20][CH:19]=[CH:18][CH:17]=3)[CH2:4][CH2:3][N:39]2[CH2:36][CH:37]=[CH2:38])[CH:14]=[CH:13][CH:12]=[CH:11][CH:10]=1

Participants

12

Reactant 8

HCID 313Hydrochloric AcidHCID 3776IsopropanolHCID 7853AllylamineHCID 8471TriethylamineHCID 10340Sodium CarbonateHCID 14798Sodium HydroxideHCID 31297Methanesulfonyl chlorideHCID 68577114HCID 68577114, compound

Product 1

HCID 68577108HCID 68577108, compoundYield 71%

Reagents, catalysts & solvents 3

HCID 962WaterSolventHCID 1140TolueneSolventHCID 8857Ethyl AcetateSolvent

Conditions

Temperature
5 °C

Procedure

To (R)-2-[(2-hydroxyethyl)(phenylmethyl)amino]-1-phenyl-1-ethanol hydrochloride (4.00 g, 12.7 mmol) produced in Example 8, distilled water (40 mL), toluene (40 mL) and 30 wt % aqueous solution of sodium hydroxide (1.70 g, 1.0 equivalent) were added. The mixture was stirred. After the organic layer and aqueous layer were separated, the organic layer was washed twice with distilled water (20 mL), then concentrated and dried under vacuum, to obtain 3.95 g of a concentrate. Ethyl acetate (13.22 g) and triethylamine (4.50 g, 3.5 equivalents) were added to the concentrate, and the mixture was cooled to 5° C. Methanesulfonyl chloride (4.66 g, 3.2 equivalents) was added dropwise thereto, and then allylamine (4.34 g, 6.0 equivalents) was added dropwise thereto. The mixture was stirred for 1 hour. The temperature of the mixture was raised to 25° C., and then the mixture was stirred for 4 hours. To the mixture, 10 wt % aqueous solution of sodium carbonate (21.54 g) was added. After the organic layer and aqueous layer were separated, the organic layer was washed twice with distilled water (20 mL). The organic layer was concentrated. The obtained concentrate was dissolved by adding ethyl acetate (20 mL). To the solution, 28 wt % hydrogen chloride solution in isopropanol (3.60 g, 2.2 equivalents) was added to precipitate crystals. The mixture was stirred at 25° C. for 1 hour. The crystals were separated by filtration under reduced pressure, washed with isopropanol (50 mL), and dried under vacuum, to obtain 2.96 g of the title compound as white crystals (yield: 71%, chemical purity: 98.4 area %). The retention time in the chemical purity analysis method was 7.9 min.

Workup

  1. additionwere added
  2. customAfter the organic layer and aqueous layer were separated
  3. washthe organic layer was washed twice with distilled water (20 mL)
  4. concentrationconcentrated
  5. customdried under vacuum
  6. customto obtain 3.95 g of a concentrate
  7. stirringThe mixture was stirred for 1 hour
  8. temperatureThe temperature of the mixture was raised to 25° C.
  9. stirringthe mixture was stirred for 4 hours
  10. customAfter the organic layer and aqueous layer were separated
  11. washthe organic layer was washed twice with distilled water (20 mL)
  12. concentrationThe organic layer was concentrated
  13. concentrationThe obtained concentrate
  14. dissolutionwas dissolved
  15. additionby adding ethyl acetate (20 mL)
  16. customto precipitate crystals
  17. stirringThe mixture was stirred at 25° C. for 1 hour
  18. customThe crystals were separated by filtration under reduced pressure
  19. washwashed with isopropanol (50 mL)
  20. customdried under vacuum

Sources & evidence

ORD record
ord-119f56d4892541b7bc0def22963e16ec
Source dataset
uspto-grants-2012_09
Patent number
US08273883B2

Reaction notes

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