N-Methylbenzeneethanamine → N-methyl-N-((1R)-1-(N-methyl-N-phenethylcarbamoyl)-2-(2-naphthyl)ethyl)carbamic acid tert-butylester

HRID 366100

Reaction equation

HRID 366100 reaction equation
[C:1]([O:5][C:6]([N:8]([C@H:10]([CH2:14][C:15]1[CH:24]=[CH:23][C:22]2[C:17](=[CH:18][CH:19]=[CH:20][CH:21]=2)[CH:16]=1)[C:11]([OH:13])=O)[CH3:9])=[O:7])([CH3:4])([CH3:3])[CH3:2].OC1C2N=NNC=2N=CC=1.Cl.CN(C)CCCN=C=NCC.[CH3:47][NH:48][CH2:49][CH2:50][C:51]1[CH:56]=[CH:55][CH:54]=[CH:53][CH:52]=1.S([O-])(O)(=O)=O.[Na+]>CN(C)C=O.ClCCl.O.C(OCC)(=O)C>[C:1]([O:5][C:6](=[O:7])[N:8]([CH3:9])[C@@H:10]([C:11](=[O:13])[N:48]([CH3:47])[CH2:49][CH2:50][C:51]1[CH:56]=[CH:55][CH:54]=[CH:53][CH:52]=1)[CH2:14][C:15]1[CH:24]=[CH:23][C:22]2[C:17](=[CH:18][CH:19]=[CH:20][CH:21]=2)[CH:16]=1)([CH3:2])([CH3:3])[CH3:4]

Participants

10

Reactant 5

HCID 11503N-MethylbenzeneethanamineHCID 516919Sodium BisulfateHCID 27239391,3-Propanediamine, N'-(ethylcarbonimidoyl)-N,N-dimethyl-, monohydrochlorideHCID 10065151(2R)-2-[methyl-[(2-methylpropan-2-yl)oxycarbonyl]amino]-3-naphthalen-2-ylpropanoic acidHCID 1785164692,3-dihydrotriazolo[4,5-b]pyridin-7-one

Product 1

HCID 54018836N-methyl-N-((1R)-1-(N-methyl-N-phenethylcarbamoyl)-2-(2-naphthyl)ethyl)carbamic acid tert-butylesterYield 98.4%

Reagents, catalysts & solvents 4

HCID 962WaterSolventHCID 6228DimethylformamideSolventHCID 6344DichloromethaneSolventHCID 8857Ethyl AcetateSolvent

Conditions

Temperature
0 °C

Procedure

(2R)-2-(N-tert-Butoxycarbonyl-N-methylamino)-3-(2-naphthyl)propionic acid (1.40 g, 4.3 mmol) was dissolved in N,N-dimethylformamide (5 ml) and dichloromethane (5 mL). Hydroxy-7-azabenzotriazole (0.59 g, 4.3 mmol) was added as a solid. The solution was cooled to 0 ° C. N-(3-dimethylaminopropyl)-N'-ethylcarbodiimide hydrochloride (0.99 g, 5.2 mmol) was added. The solution was stirred for 20 min at 0° C. N-Methyl-N-phenethylamine (0.86 ml, 6.0 mmol) was added. The solution was stirred for 16 h, while it was warming up to room temperature. It was diluted with water (300 ml) and ethyl acetate (150 ml). 10% sodium hydrogen sulfate solution (80 ml) was added. The phases were seperated. The aqueous phase was extracted with ethyl acetate (4×50 ml). The combined organic layers were washed with saturated sodium hydrogen carbonate solution (200 ml) and dried over magensium sulfate. The solvent was removed in vacuo. The crude product was purified by flash chromatography on silica (90 g), using ethyl acetate/heptane 1:1 as eluent to give 1.89 g of N-methyl-N-((1R)-1-(N-methyl-N-phenethylcarbamoyl)-2-(2-naphthyl)ethyl)carbamic acid tert-butylester.

Workup

  1. stirringThe solution was stirred for 16 h, while it
  2. temperaturewas warming up to room temperature
  3. customThe phases were seperated
  4. extractionThe aqueous phase was extracted with ethyl acetate (4×50 ml)
  5. washThe combined organic layers were washed with saturated sodium hydrogen carbonate solution (200 ml)
  6. dry with materialdried over magensium sulfate
  7. customThe solvent was removed in vacuo
  8. customThe crude product was purified by flash chromatography on silica (90 g)

Sources & evidence

ORD record
ord-534d9eb613d54cb6bab722f65e27362d
Source dataset
uspto-grants-2000_10
Patent number
US06127354

Linked notes

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