Hydrochloric Acid → HCID 68539667, compound

HRID 1994301Notes

Reaction equation

HRID 1994301 reaction equation
[CH3:1][O:2][C:3]1[CH:8]=[CH:7][C:6]([CH:9]2[CH2:13]OS(=O)(=O)[N:10]2[CH:16]([CH:24]([CH3:26])[CH3:25])[C:17]([O:19]C(C)(C)C)=[O:18])=[CH:5][CH:4]=1.[CH2:27]([NH2:34])[C:28]1[CH:33]=[CH:32][CH:31]=[CH:30][CH:29]=1.[C:35]([O-])([O-])=[O:36].[Cs+].[Cs+].C(Cl)(Cl)=O.Cl>CCOC(C)=O.C(#N)C>[CH2:27]([N:34]1[CH2:13][CH:9]([C:6]2[CH:5]=[CH:4][C:3]([O:2][CH3:1])=[CH:8][CH:7]=2)[N:10]([CH:16]([CH:24]([CH3:25])[CH3:26])[C:17]([OH:19])=[O:18])[C:35]1=[O:36])[C:28]1[CH:33]=[CH:32][CH:31]=[CH:30][CH:29]=1

Participants

8

Reactant 5

HCID 313Hydrochloric AcidHCID 6371PhosgeneHCID 7504BenzylamineHCID 10796Cesium carbonateHCID 86619840HCID 86619840, compound

Product 1

HCID 68539667HCID 68539667, compoundYield 50.1%

Reagents, catalysts & solvents 2

HCID 6342AcetonitrileSolventHCID 8857Ethyl AcetateSolvent

Conditions

Temperature
55 °C

Procedure

t-Butyl 2-(4-(4-methoxyphenyl)-2,2-dioxo-(1,2,3) oxathiazolidin-3-yl)-3-methylbutyrate (0.30 g; 0.778 mmol) was introduced into acetonitrile (5 ml). Benzylamine (0.10 g; 0.93 mmol) and Cs2CO3 (0.50 g; 1.55 mmol) were added thereto, and the reaction mixture was stirred at 55° C. for 5 h. It was then filtered through kieselguhr, and the residue was washed with a solution of methanol (3%) in acetonitrile. The filtrate was concentrated in a rotary evaporator, and the residue was taken up in dioxane (10 ml) and concentrated aqueous H2SO4 (10 ml). The mixture was stirred at 70° C. for 2 h and then evaporated to dryness in a rotary evaporator. The residue was taken up in toluene, and 1N NaOH (10 ml) was added. After the reaction mixture had been cooled to 0° C., phosgene (20% in toluene; 0.58 ml; 1.16 mmol) was slowly added dropwise. The mixture was then stirred at 0° C. for 2 h. The reaction mixture was adjusted to pH 1-2 with dilute aqueous HCl, mixed with EtOAc and extracted with EtOAc (2×). The combined organic phases were dried over MgSO4, and the solvent was removed in a rotary evaporator. Purification by column chromatography (CH2Cl2/MeOH, gradient) resulted in 2-(3-benzyl-5-(4-methoxyphenyl)-2-oxoimidazolidin-1-yl)-3-methylbutyric acid (0.15 g; 0.39 mmol). MS: 383.15 (M+H); Rt: 1.52 min (method: gradient 0 min 96% H2O (0.05% TFA) 2.0 min 95% acetonitrile, 95% acetonitrile to 2.4 min, 4% acetonitrile 2.45 min; flow rate 1 ml/min; column 0.4 μL (YMC J'sphere ODS H80 20X2 1.4μ); 30° C.)

Workup

  1. filtrationIt was then filtered through kieselguhr
  2. washthe residue was washed with a solution of methanol (3%) in acetonitrile
  3. concentrationThe filtrate was concentrated in a rotary evaporator
  4. stirringThe mixture was stirred at 70° C. for 2 h
  5. customevaporated to dryness in a rotary evaporator
  6. addition1N NaOH (10 ml) was added
  7. temperatureAfter the reaction mixture had been cooled to 0° C.
  8. stirringThe mixture was then stirred at 0° C. for 2 h
  9. extractionextracted with EtOAc (2×)
  10. dry with materialThe combined organic phases were dried over MgSO4
  11. customthe solvent was removed in a rotary evaporator
  12. customPurification by column chromatography (CH2Cl2/MeOH, gradient)

Sources & evidence

ORD record
ord-a11920ec5448421dbfb4b6f9fe5371db
Source dataset
uspto-grants-2010_01
Patent number
US07652143B2

Reaction notes

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