Ethyl isocyanate → (rac)-4-(4-Cyanophenyl)-5,6,7,8-tetrahydroisoquinolin-8-yl ethylcarbamate

HRID 714071Notes

Reaction equation

HRID 714071 reaction equation
[OH:1][CH:2]1[C:11]2[CH:10]=[N:9][CH:8]=[C:7]([C:12]3[CH:19]=[CH:18][C:15]([C:16]#[N:17])=[CH:14][CH:13]=3)[C:6]=2[CH2:5][CH2:4][CH2:3]1.[CH2:20]([N:22]=[C:23]=[O:24])[CH3:21].CCN(CC)CC.C([O-])(O)=O.[Na+]>C(Cl)Cl.CN(C1C=CN=CC=1)C.CO>[CH2:20]([NH:22][C:23](=[O:24])[O:1][CH:2]1[C:11]2[CH:10]=[N:9][CH:8]=[C:7]([C:12]3[CH:13]=[CH:14][C:15]([C:16]#[N:17])=[CH:18][CH:19]=3)[C:6]=2[CH2:5][CH2:4][CH2:3]1)[CH3:21]

Participants

8

Reactant 4

HCID 8022Ethyl isocyanate3×HCID 8471Triethylamine3×HCID 516892Sodium BicarbonateHCID 71811404(rac)-4-(8-Hydroxy-5,6,7,8-tetrahydroisoquinolin-4-yl)benzonitrile

Product 1

HCID 71811405(rac)-4-(4-Cyanophenyl)-5,6,7,8-tetrahydroisoquinolin-8-yl ethylcarbamateYield 51.3%

Reagents, catalysts & solvents 3

HCID 142844-(Dimethylamino)pyridineCatalystHCID 887MethanolSolventHCID 6344DichloromethaneSolvent

Procedure

A cooled (0° C.) solution of (rac)-4-(8-hydroxy-5,6,7,8-tetrahydroisoquinolin-4-yl)benzonitrile (example 11) (50 mg, 200 μmol) in CH2Cl2 (1.4 mL) was treated with ethyl isocyanate (24.8 μL, 300 μmol) and Et3N (24.8 μL, 300 μmol). After stirring 1 night at room temperature and 1 h at reflux again ethyl isocyanate (24.8 μL, 300 μmol) and Et3N (24.8 μL, 300 μmol) were added. The solution was refluxed for 9 h, treated again with ethyl isocyanate (24.8 μL, 300 μmol), Et3N (24.8 μL, 300 μmol) and DMAP (2.4 mg, 20 μmol). After 1 night at room temperature MeOH (2 mL) was added. The reaction mixture was poured on aq. sat. NaHCO3 solution followed by extraction with AcOEt (3×). The organic phases were washed once with aq. sat. NaCl solution. The combined organic phases were dried (Na2SO4), filtered and purified by flash chromatography (50 g SiO2, Telos-cartridge, CH2Cl2/MeOH 1%). Precipitation from CH2Cl2 with n-pentane gave the title compound (33 mg, 51%) as off-white foam. MS: 322.2 (M+H+).

Workup

  1. additionwere added
  2. temperatureThe solution was refluxed for 9 h
  3. extractionfollowed by extraction with AcOEt (3×)
  4. washThe organic phases were washed once with aq. sat. NaCl solution
  5. dry with materialThe combined organic phases were dried (Na2SO4)
  6. filtrationfiltered
  7. custompurified by flash chromatography (50 g SiO2, Telos-cartridge, CH2Cl2/MeOH 1%)
  8. customPrecipitation from CH2Cl2 with n-pentane

Sources & evidence

ORD record
ord-29613073ec1d4de7b362b7b6e0b453c9
Source dataset
uspto-grants-2015_11
Patent number
US09187429B2

Reaction notes

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