Iodine → N-((1R)-1-aminomethyl-2-phenylethyl)-N-methylcarbamic acid tert-butylester

HRID 1268630Notes

Reaction equation

HRID 1268630 reaction equation
[C:1]([O:5][C:6](=[O:20])[N:7]([C@@H:9]([C:17](=O)[NH2:18])[CH2:10][C:11]1[CH:16]=[CH:15][CH:14]=[CH:13][CH:12]=1)[CH3:8])([CH3:4])([CH3:3])[CH3:2].[BH4-].[Na+].II.[Cl-].[NH4+].[OH-].[Na+]>O1CCCC1.O>[C:1]([O:5][C:6](=[O:20])[N:7]([C@@H:9]([CH2:17][NH2:18])[CH2:10][C:11]1[CH:16]=[CH:15][CH:14]=[CH:13][CH:12]=1)[CH3:8])([CH3:2])([CH3:4])[CH3:3]

Participants

8

Reactant 5

HCID 807IodineHCID 14798Sodium HydroxideHCID 25517Ammonium ChlorideHCID 4311764Sodium borohydrideHCID 54512009N-((1R)-1-carbamoyl-2-phenylethyl)-N-methylcarbamic acid tert.-butylester

Product 1

HCID 53810010N-((1R)-1-aminomethyl-2-phenylethyl)-N-methylcarbamic acid tert-butylesterYield 17.5%

Reagents, catalysts & solvents 2

HCID 962WaterSolventHCID 8028TetrahydrofuranSolvent2×

Conditions

Temperature
5 °C

Procedure

N-((1R)-1-Carbamoyl-2-phenylethyl)-N-methylcarbamic acid tert.-butylester (2.73 g, 9.81 mmol) was dissolved in tetrahydrofuran (10 ml). The solution was cooled to 5° C. A suspension of sodium borohydride (816 mg, 21.58 mmol) in tetrahydrofuran (10 ml) was added. A solution of iodine (1.24 g, 4.91 mmol) was added dropwise. After the addition was completed, the solution was heated to reflux for 16 h. It was cooled to 5° C. A 10% solution of ammonium chloride in water (60 ml) was added dropwise. The solution was warmed to 50° C. for 1 h. It was cooled to room temperature. 1 N sodium hydroxide solution was added until pH 14. It was extracted with tert-butyl methyl ether (4×100 ml). The combined organic layers were dried over magnesium sulfate. The solvent was removed in vacuo. The crude product was purified by flash chromatography on silica (150 g) using dichloromethane/methanol/25% aqueous ammonia 100:10:1 as eluent to give 453 mg of N-((1R)-1-aminomethyl-2-phenylethyl)-N-methylcarbamic acid tert-butylester.

Workup

  1. additionwas added
  2. additionAfter the addition
  3. temperaturethe solution was heated
  4. temperatureto reflux for 16 h
  5. temperatureIt was cooled to 5° C
  6. temperatureThe solution was warmed to 50° C. for 1 h
  7. temperatureIt was cooled to room temperature
  8. extractionIt was extracted with tert-butyl methyl ether (4×100 ml)
  9. dry with materialThe combined organic layers were dried over magnesium sulfate
  10. customThe solvent was removed in vacuo
  11. customThe crude product was purified by flash chromatography on silica (150 g)

Sources & evidence

ORD record
ord-e60a8c82590e480b9c4e3b82d21879b6
Source dataset
uspto-grants-2003_04
Patent number
US06555570B2

Reaction notes

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