Tetrahydrofuran → (αR)-3-Chloro-α-methyl-6-isoquinolinemethanol

HRID 1427769Notes

Reaction equation

HRID 1427769 reaction equation
[Cl:1][C:2]1[N:3]=[CH:4][C:5]2[C:10]([CH:11]=1)=[CH:9][C:8]([C:12](=[O:14])[CH3:13])=[CH:7][CH:6]=2.C([O-])=O.[Na+].O1CCCC1>O.CC1C=CC(C(C)C)=CC=1.CC1C=CC(C(C)C)=CC=1.Cl[Ru]Cl.Cl[Ru]Cl.CC1C=CC(S(N[C@@H]([C@H](N)C2C=CC=CC=2)C2C=CC=CC=2)(=O)=O)=CC=1>[Cl:1][C:2]1[N:3]=[CH:4][C:5]2[C:10]([CH:11]=1)=[CH:9][C:8]([C@H:12]([OH:14])[CH3:13])=[CH:7][CH:6]=2

Participants

7

Reactant 3

HCID 8028TetrahydrofuranHCID 2723810Sodium FormateHCID 866758631-(3-Chloroisoquinolin-6-yl)ethanone

Product 1

HCID 86675864(αR)-3-Chloro-α-methyl-6-isoquinolinemethanolYield 92.9%

Reagents, catalysts & solvents 3

HCID 2734565N-((1R,2R)-2-Amino-1,2-diphenylethyl)-4-methylbenzene-1-sulfonamideCatalystHCID 10908223Dichloro(p-cymene)ruthenium(II) dimerCatalystHCID 962WaterSolvent

Conditions

Temperature
70 °C

Procedure

Dichloro(p-cymene)ruthenium(II) dimer (3 mg, 0.005 mmol) and (1R,2R)-(−)-N-p-tosyl-1,2-diphenylethylenediamine (4.4 mg, 0.012 mmol) was suspended in degassed water (2 mL) and the mixture was degassed with nitrogen for 15 minutes. The mixture was stirred at 70° C. under nitrogen for 90 minutes. The resulting yellow solution was cooled to room temperature. 1-(3-Chloro-isoquinolin-6-yl)-ethanone (206 mg, 1 mmol), sodium formate (340 mg, 5 mmol) and degassed tetrahydrofuran (1 mL) were added and the reaction mixture was degassed with nitrogen for 5 minutes. The reaction mixture was vigorously stirred at 40° C. for 2.5 hours. The reaction mixture was cooled to room temperature and was extracted with ethyl acetate. The organic layer was separated, washed with water and brine, dried over sodium sulfate, filtered and evaporated. The residue was purified by silica gel chromatography using a gradient of iso-hexanes/ethyl acetate 4:1 to 2:1 to afford the title compound (193 mg, 92%) as a white solid. 1H NMR (300 MHz, CDCl3) δ1.60 (d, J=5.9 Hz, 3H), 2.14 (d, J=3.1 Hz, 1H), 5.08-5.16 (m, 1H), 7.63 (dd, J=8.6, 1.6 Hz, 1H), 7.72 (s, 1H), 7.77 (brs, 1H), 7.96 (d, J=8.6 Hz, 1H), 9.04 (s, 1H). LCMS (m/z) 208/210 [M+H], Tr=4.25 min.

Workup

  1. customthe mixture was degassed with nitrogen for 15 minutes
  2. temperatureThe resulting yellow solution was cooled to room temperature
  3. additionwere added
  4. customthe reaction mixture was degassed with nitrogen for 5 minutes
  5. stirringThe reaction mixture was vigorously stirred at 40° C. for 2.5 hours
  6. temperatureThe reaction mixture was cooled to room temperature
  7. extractionwas extracted with ethyl acetate
  8. customThe organic layer was separated
  9. washwashed with water and brine
  10. dry with materialdried over sodium sulfate
  11. filtrationfiltered
  12. customevaporated
  13. customThe residue was purified by silica gel chromatography

Sources & evidence

ORD record
ord-8abb9baf1d004c43b619afba1f480e33
Source dataset
uspto-grants-2015_01
Patent number
US08933015B2

Reaction notes

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