Methyl iodide → HCID 67777296, compound

HRID 2065779Notes

Reaction equation

HRID 2065779 reaction equation
[CH2:1]([N:8]([C@H:14]([C:16]1[CH:21]=[CH:20][CH:19]=[CH:18][CH:17]=1)[CH3:15])[C@@H:9]([CH3:13])[CH2:10][CH2:11][OH:12])[C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][CH:3]=1.[H-].[Na+].[CH3:24]I>C1COCC1>[CH2:1]([N:8]([C@H:14]([C:16]1[CH:17]=[CH:18][CH:19]=[CH:20][CH:21]=1)[CH3:15])[C@H:9]([CH2:10][CH2:11][O:12][CH3:24])[CH3:13])[C:2]1[CH:3]=[CH:4][CH:5]=[CH:6][CH:7]=1

Participants

5

Reactant 3

HCID 6328Methyl iodideHCID 24758Sodium hydrideHCID 67777569HCID 67777569, compound

Product 1

HCID 67777296HCID 67777296, compoundYield 81.3%

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent

Conditions

Temperature
0 °C

Procedure

(3S)-3-[Benzyl-[(1S)-1-phenylethyl]amino]butan-1-ol (17.54 g, 61.9 mmol) is dissolved in anhydrous THF (186 mL) and cooled to 0° C. under an argon atmosphere. Sodium hydride (4.95 g, 60% suspension in mineral oil, 123.8 mmol) is added portionwise over 10 min. The mixture is stirred at 0° C. for 15 min, and then allowed to warm to RT. Methyl iodide (10.54 g, 74.28 mmol) is added dropwise over 30 min. After stirring for 30 additional min, the reaction is quenched by the addition of a saturated solution of NH4Cl in water. The layers are separated and the aqueous layer is extracted with diethyl ether (2×100 mL). The combined organic layers are dried over MgSO4, concentrated, and the crude is purified by normal phase chromatography (two 120 g silica-gel cartridges, 10% of methyl tert-butyl ether in hexanes) to afford the title compound as a colorless oil (14.96 g, 81%). LC-ES/MS m/z 298 (M+1).

Workup

  1. temperatureto warm to RT
  2. stirringAfter stirring for 30 additional min
  3. customthe reaction is quenched by the addition of a saturated solution of NH4Cl in water
  4. customThe layers are separated
  5. extractionthe aqueous layer is extracted with diethyl ether (2×100 mL)
  6. dry with materialThe combined organic layers are dried over MgSO4
  7. concentrationconcentrated
  8. customthe crude is purified by normal phase chromatography (two 120 g silica-gel cartridges, 10% of methyl tert-butyl ether in hexanes)

Sources & evidence

ORD record
ord-215193236094495da03258232a2548e5
Source dataset
uspto-grants-2012_10
Patent number
US08288548B2

Reaction notes

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