Acetic Acid → Boc-Ile-OSu

HRID 1482160Notes

Reaction equation

HRID 1482160 reaction equation
[NH:1]([C:10]([O:12][C:13]([CH3:16])([CH3:15])[CH3:14])=[O:11])[C@H:2]([C:7]([OH:9])=[O:8])[C@H:3]([CH2:5][CH3:6])[CH3:4].C1CC[CH:20]([N:23]=C=NC2CCCCC2)[CH2:19]C1.[C:32]([OH:35])(=O)[CH3:33].[OH:36]S([O-])(=O)=O.[K+].[Na+].[Cl-].C([O-])([O-])=O.[Na+].[Na+]>C(OCC)(=O)C.O>[NH:1]([C:10]([O:12][C:13]([CH3:14])([CH3:16])[CH3:15])=[O:11])[C@H:2]([C:7]([O:9][N:23]1[C:32](=[O:35])[CH2:33][CH2:19][C:20]1=[O:36])=[O:8])[C@H:3]([CH2:5][CH3:6])[CH3:4]

Participants

9

Reactant 6

HCID 176Acetic AcidHCID 5234Sodium Chloride3×HCID 10340Sodium CarbonateHCID 10868DicyclohexylcarbodiimideHCID 516920Potassium bisulfateHCID 2724762tert-Butoxycarbonyl-L-isoleucine

Product 1

HCID 333451Boc-Ile-OSuYield 89%

Reagents, catalysts & solvents 2

HCID 962WaterSolventHCID 8857Ethyl AcetateSolvent2×

Conditions

Temperature
0 °C

Procedure

Under stirring, 1.00 equivalent of Boc-Ile-OH.1/2 H2O (Mw=240.3) and 1.05 equivalents of Suc-OH (Mw=115) were added to ethyl acetate. The solution was cooled to 0±5° C. and then 1.10 equivalents DCC (Mw=206.3) diluted in ethyl acetate was poured into the solution. The suspension was stirred at 0° C. for at least 30 min and at room temperature for at least 5 hours. After the reaction mixture had been quenched by adding 2.4 g acetic acid (0.20 equivalents), the DCU was filtered and washed twice with ethyl acetate. The organic layers were washed with 5% (weight) aqueous NaCl solution containing 0.5 equivalents KHSO4, 5% (weight) aqueous NaCl solution; 5% (weight) aqueous NaCl solution containing 0.5 equivalents Na2CO3 and finally with 5% (weight) aqueous NaCl solution. The solvent was concentrated in vacuo. The concentrated solution was twice taken up in ethyl acetate and further evaporated in vacuo in order to eliminate the remaining water. The concentrated organic layer was diluted with cyclohexane or heptane. The precipitated suspension was stirred at room temperature for at least 30 min, filtered and finally dried under vacuum (45° C.). The dried precipitate yielded 89% (based on NMR content) of Boc-Ile-OSu as white solid.

Workup

  1. additionwas poured into the solution
  2. stirringThe suspension was stirred at 0° C. for at least 30 min and at room temperature for at least 5 hours
  3. customAfter the reaction mixture had been quenched
  4. filtrationthe DCU was filtered
  5. washwashed twice with ethyl acetate
  6. washThe organic layers were washed with 5% (weight) aqueous NaCl solution
  7. concentrationThe solvent was concentrated in vacuo
  8. customfurther evaporated in vacuo in order
  9. additionThe concentrated organic layer was diluted with cyclohexane or heptane
  10. stirringThe precipitated suspension was stirred at room temperature for at least 30 min
  11. filtrationfiltered
  12. customfinally dried under vacuum (45° C.)

Sources & evidence

ORD record
ord-a8359f0ffae84cc680d124a286b24e51
Source dataset
uspto-grants-2016_08
Patent number
US09409946B2

Reaction notes

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