Iodine → (R)-5-tert-butyl-3-((tetrahydrofuran-2-yl)methyl)thiazol-2(3H)-imine hydroiodide

HRID 82760

Reaction equation

HRID 82760 reaction equation
[CH3:1][C:2]([CH3:7])([CH3:6])[CH2:3][CH:4]=O.[O:8]1[CH2:12][CH2:11][CH2:10][C@@H:9]1[CH2:13][NH2:14].[S-:15][C:16]#[N:17].[K+].[I:19]I.S(S([O-])=O)([O-])(=O)=O.[Na+].[Na+]>C(#N)C.C(OCC)(=O)C.ClCCl>[IH:19].[C:2]([C:3]1[S:15][C:16](=[NH:17])[N:14]([CH2:13][C@H:9]2[CH2:10][CH2:11][CH2:12][O:8]2)[CH:4]=1)([CH3:7])([CH3:6])[CH3:1]

Participants

9

Reactant 5

HCID 807IodineHCID 763353,3-DimethylbutanalHCID 516872Potassium thiocyanateHCID 656671Sodium PyrosulfiteHCID 2734124(R)-(-)-Tetrahydrofurfurylamine

Product 1

HCID 67303544(R)-5-tert-butyl-3-((tetrahydrofuran-2-yl)methyl)thiazol-2(3H)-imine hydroiodideYield 50%

Reagents, catalysts & solvents 3

HCID 6342AcetonitrileSolventHCID 6344DichloromethaneSolventHCID 8857Ethyl AcetateSolvent

Procedure

To a solution of 3,3-dimethylbutanal (9.90 g, 99 mmol) in acetonitrile (60 mL) were added molecular sieves (8 g) and (R)-(tetrahydrofuran-2-yl)methanamine (10 g, 99 mmol). The reaction mixture was stirred at room temperature for 24 hours and then filtered through celite. To the filtrate was added potassium thiocyanate (12.78 g, 131 mmol). The temperature was adjusted to 50° C. and the mixture was stirred until the solids were dissolved. Then, iodine (25.09 g, 99 mmol) was added to the mixture and stirred at 50° C. for 24 hours. The reaction mixture was cooled, and to the mixture was added sodium meta-bisulfite 20% (100 mL) and stirred for 30 min. The organic layers were separated and the aqueous layer was washed with dichloromethane (3×40 mL). The combined organic extracts were dried with sodium sulfate, filtered and concentrated to obtain the crude product as a yellow solid. The residue was taken into dichloromethane (20 mL) and ethyl acetate (80 mL), the mixture was warmed to 40° C., sonicated, and cooled to between 0-10° C. The solid was collected and washed with cold ethyl acetate to obtain the title compound (18.2 g, 50%). 1H NMR (300 MHz, DMSO-d6) δ ppm 1.27 (s, 9 H) 1.48-1.61 (m, 1 H) 1.78-1.93 (m, 2 H) 1.94-2.07 (m, 1 H) 3.62-3.71 (m, 1 H) 3.76-3.84 (m, 1 H) 3.92-4.08 (m, 2 H) 4.11-4.20 (m, 1 H) 7.19 (s, 1 H) 9.39 (s, 2 H); MS (DCI/NH3) m/z 241 (M+H)+.

Workup

  1. filtrationfiltered through celite
  2. customwas adjusted to 50° C.
  3. stirringthe mixture was stirred until the solids
  4. dissolutionwere dissolved
  5. stirringstirred at 50° C. for 24 hours
  6. temperatureThe reaction mixture was cooled
  7. stirringstirred for 30 min
  8. customThe organic layers were separated
  9. washthe aqueous layer was washed with dichloromethane (3×40 mL)
  10. dry with materialThe combined organic extracts were dried with sodium sulfate
  11. filtrationfiltered
  12. concentrationconcentrated
  13. customto obtain the crude product as a yellow solid
  14. temperaturethe mixture was warmed to 40° C.
  15. customsonicated
  16. temperaturecooled to between 0-10° C
  17. customThe solid was collected
  18. washwashed with cold ethyl acetate

Sources & evidence

ORD record
ord-a54879990eb046459585e8f2bd139441
Source dataset
uspto-grants-2014_09
Patent number
US08846730B2

Linked notes

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