Hydrochloric Acid → HCID 86666178, compound

HRID 2065796Notes

Reaction equation

HRID 2065796 reaction equation
C1N=CN([C:6]([N:8]2C=N[CH:10]=[CH:9]2)=[S:7])C=1.[CH3:13][O:14][CH2:15][CH2:16][C@@H](N)C.Cl.S([O-])([O-])(=O)=S.[Na+].[Na+]>C(OC)(C)(C)C.C1COCC1>[N:8]([C@@H:9]([CH3:10])[CH2:16][CH2:15][O:14][CH3:13])=[C:6]=[S:7]

Participants

7

Reactant 4

HCID 313Hydrochloric AcidHCID 24477Sodium ThiosulfateHCID 802641,1'-ThiocarbonyldiimidazoleHCID 28937401HCID 28937401, compound

Product 1

HCID 86666178HCID 86666178, compoundYield 83.2%

Reagents, catalysts & solvents 2

HCID 8028TetrahydrofuranSolventHCID 15413tert-Butyl methyl etherSolvent

Conditions

Temperature
-5 °C

Procedure

Under a nitrogen atmosphere N,N-thiocarbonyldiimidazole (97.0 g, 0.55 mol) and THF (470 mL) are added and the mixture is stirred for 15-30 min. The mixture is cooled to −10 to 0° C., a solution of (S)-4-methoxybutan-2-amine (46.9 g, 0.455 mol) in methyl tert-butyl ether (389 mL) is added, and the reaction mixture is warmed to 10-20° C. The reaction mixture is stirred at this temperature for 15-20 h, and then is cooled to 0-10° C. Hydrochloric acid (275 mL, 4 N in water) is added to arrive at a pH of 1 to 2. The reaction mixture is warmed to RT and the layers are separated. The aqueous layer is extracted with ethyl acetate (235 mL) and the organic layers are combined and washed with water (140 mL). The organic solution is concentrated under reduced pressure below 45° C., ethyl acetate (211.5 mL) is added, and the solution is concentrated under reduced pressure below 45° C. twice, and ethyl acetate (235 mL) is added. Sodium thiosulfate (32.3 g, 227.0 mmol) is added, the solution is filtered, and the filtercake is washed with ethyl acetate (104 mL). The filtrate is concentrated under reduced pressure below 45° C. to furnish the title compound as a yellow oil (55.0 g, 77%).

Workup

  1. temperaturethe reaction mixture is warmed to 10-20° C
  2. stirringThe reaction mixture is stirred at this temperature for 15-20 h
  3. temperatureis cooled to 0-10° C
  4. temperatureThe reaction mixture is warmed to RT
  5. customthe layers are separated
  6. extractionThe aqueous layer is extracted with ethyl acetate (235 mL)
  7. washwashed with water (140 mL)
  8. concentrationThe organic solution is concentrated under reduced pressure below 45° C., ethyl acetate (211.5 mL)
  9. additionis added
  10. concentrationthe solution is concentrated under reduced pressure below 45° C. twice
  11. additionethyl acetate (235 mL) is added
  12. filtrationthe solution is filtered
  13. washthe filtercake is washed with ethyl acetate (104 mL)
  14. concentrationThe filtrate is concentrated under reduced pressure below 45° C.

Sources & evidence

ORD record
ord-ee53fe02e01a495a81a5c633cc6df7df
Source dataset
uspto-grants-2012_10
Patent number
US08288548B2

Reaction notes

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