Methyl iodide → HCID 44596484, compound

HRID 386491Notes

Reaction equation

HRID 386491 reaction equation
[CH:1]1([C@H:4]([NH:7][C@H:8]([C:10]2[CH:15]=[CH:14][CH:13]=[CH:12][CH:11]=2)[CH3:9])[CH2:5][OH:6])[CH2:3][CH2:2]1.[H-].[Na+].[CH3:18]I>C1COCC1>[CH:1]1([C@H:4]([NH:7][C@H:8]([C:10]2[CH:11]=[CH:12][CH:13]=[CH:14][CH:15]=2)[CH3:9])[CH2:5][O:6][CH3:18])[CH2:3][CH2:2]1

Participants

5

Reactant 3

HCID 6328Methyl iodideHCID 24758Sodium hydrideHCID 44596483HCID 44596483, compound

Product 1

HCID 44596484HCID 44596484, compoundYield 85%

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent

Procedure

To a solution of (S)-2-cyclopropyl-2-[(S)-1-phenylethylamino]ethanol (29.2 g, 0.143 mol) in THF (700 mL) at 0° C. was added NaH (6.29 g, 0.157 mol, 60% dispersion in mineral oil). The cooling bath was removed and the reaction mixture was allowed to warm to room temperature and was stirred at room temperature for 30 min. Methyl iodide (20.30 g, 0.143 mol) was then added dropwise via syringe. Some warming occurred soon after the addition was complete. The temperature of the reaction mixture was controlled at ˜25° C. with a water bath containing a small amount of ice. The reaction mixture was stirred at room temperature for 4 h. The reaction mixture was then slowly quenched with saturated aqueous NaHCO3 solution and was transferred to a separatory funnel containing saturated aqueous NaHCO3 solution (400 mL). The aqueous layer was extracted with ethyl acetate (3×300 mL). The combined organic layers were washed with brine, dried over MgSO4, filtered and concentrated. The crude product was purified by column chromatography on silica gel (5% MeOH in 1:1 ethyl acetate/hexanes) to afford (5)-1-cyclopropyl-2-methoxy-N-[(S)-1-phenylethyl]-ethanamine (26.52 g, 85% yield) as a light brown oil: [α]25D −61.5 (c 0.72, CHCl3); 1H NMR (400 MHz, CDCl3) δ 7.30-7.25 (m, 4H), 7.20-7.16 (m, 1H), 3.98-3.93 (q, J=6.8 Hz, 1H), 3.50 (dd, JAB=9.5, JAX=3.5 Hz, 1H), 3.35 (s, 3H), 3.34 (dd, JBA=9.5, JBX=5.8 Hz, 1H), 1.79-1.74 (m, 2H), 1.33 (d, 6.5 Hz, 3H), 0.73-0.67 (m, 1H), 0.36-0.34 (m, 2H), 0.03-−0.06 (m, 2H); GC/MS (ESI) m/e 220.2 [(M+H)+, calcd for C14H22NO 220.2].

Workup

  1. customThe cooling bath was removed
  2. additionafter the addition
  3. customThe temperature of the reaction mixture was controlled at ˜25° C. with a water bath
  4. additioncontaining a small amount of ice
  5. stirringThe reaction mixture was stirred at room temperature for 4 h
  6. customThe reaction mixture was then slowly quenched with saturated aqueous NaHCO3 solution
  7. customwas transferred to a separatory funnel
  8. additioncontaining saturated aqueous NaHCO3 solution (400 mL)
  9. extractionThe aqueous layer was extracted with ethyl acetate (3×300 mL)
  10. washThe combined organic layers were washed with brine
  11. dry with materialdried over MgSO4
  12. filtrationfiltered
  13. concentrationconcentrated
  14. customThe crude product was purified by column chromatography on silica gel (5% MeOH in 1:1 ethyl acetate/hexanes)

Sources & evidence

ORD record
ord-5ea4f88906c44149aff9c35807fdc3d2
Source dataset
uspto-grants-2013_02
Patent number
US08372847B2

Reaction notes

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