Diisopropylethylamine → N-((1R)-2-(1,2,3,4-Tetrahydroisoquinolin-2-yl)-1-((2-naphthyl)methyl)-2-oxoethyl)-N-methylcarbamic acid tert-butyl ester

HRID 650814Notes

Reaction equation

HRID 650814 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](O)=[O:12])[CH3:9])=[O:7])([CH3:4])([CH3:3])[CH3:2].ON1[C:30]2N=[CH:32][CH:33]=[CH:34][C:29]=2N=N1.Cl.CN(C)[CH2:38][CH2:39][CH2:40][N:41]=[C:42]=NCC.C(N(C(C)C)C(C)C)C>CN(C)C=O.ClCCl.C(OCC)(=O)C>[C:1]([O:5][C:6](=[O:7])[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]([N:41]1[CH2:40][CH2:39][C:38]2[C:32](=[CH:33][CH:34]=[CH:29][CH:30]=2)[CH2:42]1)=[O:12])[CH3:9])([CH3:2])([CH3:4])[CH3:3]

Participants

8

Reactant 4

HCID 81531DiisopropylethylamineHCID 181649HOAtHCID 27239391,3-Propanediamine, N'-(ethylcarbonimidoyl)-N,N-dimethyl-, monohydrochlorideHCID 10065151(2R)-2-[methyl-[(2-methylpropan-2-yl)oxycarbonyl]amino]-3-naphthalen-2-ylpropanoic acid

Product 1

HCID 54129692N-((1R)-2-(1,2,3,4-Tetrahydroisoquinolin-2-yl)-1-((2-naphthyl)methyl)-2-oxoethyl)-N-methylcarbamic acid tert-butyl esterYield 61.2%

Reagents, catalysts & solvents 3

HCID 6228DimethylformamideSolventHCID 6344DichloromethaneSolventHCID 8857Ethyl AcetateSolvent

Conditions

Temperature
0 °C

Procedure

(2R)-2-(N-(tert-Butoxycarbonyl)-N-methylamino)-3-(2-naphthyl)propionic acid (7.41 g, 22.5 mmol) was dissolved in N,N-dimethylformamide (90 ml) and dichloromethane (110 ml). 1-Hydroxy-7-azabenzotriazole (3.06 g, 22.5 mmol) was added. The mixture was cooled to 0° C. N-(3-Dimethylaminopropyl)-N′-ethylcarbodiimide hydrochloride (4.32 g, 22.5 mmol) was added. The solution was stirred for 15 min at 0° C. 1,2,3,4-Tetrahydroqunoline (3.00 g, 22.5 mmol) and ethyldiisopropylamine (3.90 m., 22.5 mmol) were added. The reaction mixture was stirred for 16 h, while it was warming up to room temperature. It was diluted with ethyl acetate (80 ml) and extracted with 10% aquoeous sodium hydrogen sulfate solution (250 ml). The aqueous phase was extracted with ethyl acetate (3×60 ml). The combined organic layers were washed with saturated sodium hydrogen carbonate solution (200 ml) and dried over magnesium sulfate. The solvent was removed in vacuo. The crude product was purified by flash chromatography on silica (130 g), using ethyl acetateiheptane 1:2. as eluent to give 6.12 g of N-((l R)-2-(1,2,3,4-tetrahydroisoquinolin-2-yl)-1-((2-naphthyl)methyl)-2-oxoethyl)-N-methylcarbamic acid tert-butyl ester.

Workup

  1. stirringThe reaction mixture was stirred for 16 h, while it
  2. temperaturewas warming up to room temperature
  3. extractionextracted with 10% aquoeous sodium hydrogen sulfate solution (250 ml)
  4. extractionThe aqueous phase was extracted with ethyl acetate (3×60 ml)
  5. washThe combined organic layers were washed with saturated sodium hydrogen carbonate solution (200 ml)
  6. dry with materialdried over magnesium sulfate
  7. customThe solvent was removed in vacuo
  8. customThe crude product was purified by flash chromatography on silica (130 g)

Sources & evidence

ORD record
ord-2ea92351c0aa4e06b98b17c09ad4b8eb
Source dataset
uspto-grants-2001_08
Patent number
US06274584B1

Reaction notes

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