Methanol → (S)-2-methyl-1-phenyl-2-(pyridine-2-yl)propan-1-amine

HRID 575925Notes

Reaction equation

HRID 575925 reaction equation
CC([S@]([NH:7][C@@H:8]([C:18]1[CH:23]=[CH:22][CH:21]=[CH:20][CH:19]=1)[C:9]([CH3:17])([C:11]1[CH:16]=[CH:15][CH:14]=[CH:13][N:12]=1)[CH3:10])=O)(C)C.Cl.O1CCOCC1.CO.[OH-].[Na+]>ClCCl.O>[CH3:17][C:9]([C:11]1[CH:16]=[CH:15][CH:14]=[CH:13][N:12]=1)([CH3:10])[C@H:8]([C:18]1[CH:23]=[CH:22][CH:21]=[CH:20][CH:19]=1)[NH2:7]

Participants

7

Reactant 4

HCID 887MethanolHCID 14798Sodium HydroxideHCID 204431481,4-Dioxane hydrochlorideHCID 59407465(R)-2-methyl-N-((S)-2-methyl-1-phenyl-2-(pyridine-2-yl)propyl)propane-2-sulfinamide

Product 1

HCID 59407467(S)-2-methyl-1-phenyl-2-(pyridine-2-yl)propan-1-amineYield 107.2%

Reagents, catalysts & solvents 2

HCID 962WaterSolventHCID 6344DichloromethaneSolvent

Conditions

Temperature
32 °C

Procedure

To a solution of (R)-2-methyl-N—((S)-2-methyl-1-phenyl-2-(pyridin-2-yl)propyl)propane-2-sulfinamide (1200 g, 3.631 moles) dissolved in dichloromethane (12000 mL) was added 4N hydrogen chloride/dioxane solution (3000 mL, 12.00 moles) in a steady stream over a period of 1 hour at room temperature. A thick suspension formed, which was continued stirring for 1.5 hours at 32° C.; at which point Methanol (1000 mL) was added to improve stirring. After 30 minutes additional stirring, all of the solids dissolved, giving a clear amber solution and indicating complete reaction. The solvents were removed under reduced pressure leaving a gummy amber residue. The residue was taken up in distilled water (5000 mL), and the resulting solution washed with diethyl ether (2×1000 mL) to remove neutral impurities. The acidic solution was treated with solid Sodium hydroxide (400 g, 10.00 moles) until strongly basic (pH=11). The resulting aqueous mixture was extracted with dichloromethane (2×1000 mL, then 2×500 mL). The combined organic extracts were dried (anhydrous magnesium sulfate). Filtration, followed by removal of the solvent under reduced pressure, left a thick amber syrup. This residue was further dried under high vacuum to yield the crude de-protected amine (880.9 g, 107.2% of theory). 1H NMR (300 MHz, CHLOROFORM-d) δ ppm 8.64 (d, J=3.79 Hz, 1H) 7.57 (td, J=7.69, 1.90 Hz, 1H) 7.05-7.30 (m, 7H) 4.48 (s, 1H) 1.47 (br.s., 2H) 1.36 (s, 3H) 1.25 (s, 3H). MS: m/z 227.

Workup

  1. customA thick suspension formed
  2. stirringto improve stirring
  3. waitAfter 30 minutes additional stirring
  4. dissolutionall of the solids dissolved
  5. customgiving a clear amber solution
  6. customreaction
  7. customThe solvents were removed under reduced pressure
  8. customleaving a gummy amber residue
  9. washthe resulting solution washed with diethyl ether (2×1000 mL)
  10. customto remove neutral impurities
  11. extractionThe resulting aqueous mixture was extracted with dichloromethane (2×1000 mL
  12. dry with materialThe combined organic extracts were dried (anhydrous magnesium sulfate)
  13. filtrationFiltration
  14. customfollowed by removal of the solvent under reduced pressure
  15. waitleft a thick amber syrup
  16. customThis residue was further dried under high vacuum

Sources & evidence

ORD record
ord-c08ef2d9bfa448968ba8a76048ae168e
Source dataset
uspto-grants-2015_05
Patent number
US09035065B2

Reaction notes

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