Isobutyl chloroformate → Boc-Ile-Pro-OBzl

HRID 2231793Notes

Reaction equation

HRID 2231793 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)[C@H:3]([CH2:5][CH3:6])[CH3:4].C(OC(Cl)=O)C(C)C.C1C=CC2N(O)N=NC=2C=1.Cl.[NH:36]1[CH2:50][CH2:49][CH2:48][C@H:37]1[C:38]([O:40][CH2:41][C:42]1[CH:47]=[CH:46][CH:45]=[CH:44][CH:43]=1)=[O:39].C([O-])(O)=O.[Na+]>CN(C=O)C.CN1CCOCC1>[NH:1]([C:10]([O:12][C:13]([CH3:16])([CH3:15])[CH3:14])=[O:11])[C@H:2]([C:7]([N:36]1[CH2:50][CH2:49][CH2:48][C@H:37]1[C:38]([O:40][CH2:41][C:42]1[CH:43]=[CH:44][CH:45]=[CH:46][CH:47]=1)=[O:39])=[O:9])[C@H:3]([CH2:5][CH3:6])[CH3:4]

Participants

8

Reactant 5

HCID 62365Isobutyl chloroformateHCID 757711-HydroxybenzotriazoleHCID 516892Sodium BicarbonateHCID 2724762tert-Butoxycarbonyl-L-isoleucineHCID 2733413Proline benzyl ester hydrochloride

Product 1

HCID 14306235Boc-Ile-Pro-OBzlYield 92%

Reagents, catalysts & solvents 2

HCID 6228DimethylformamideSolvent2×HCID 79724-MethylmorpholineSolvent2×

Conditions

Temperature
-15 °C

Procedure

Boc-Ile-OH (12.01 g, 0.05 mole) in DMF (50 ml) was cooled to 0° C. and NMM (5.49 ml) was added. After cooling the solution to -15° C. isobutylchloroformate (6.48 ml) was added slowly while maintaining the temperature at -15° C. and stirred for 10 minutes at which time HOBt (7.65 g) was added and stirring was continued for additional 10 minutes. A pre-cooled solution of HCl-H-Pro-OBzl (12.09 g, 0.05 mole) in DMF (50 ml) and NMM (5.49 ml) was added to the above solution and the completeness of the reaction was followed by TLC. The reaction mixture was poured into a cold saturated NaHCO3 solution and stirred for one hour. The peptide was extracted into CHCl3 and washed with acid and base (0.5 N NaOH to remove HOBt), and on evaporating the solvent the product was obtained as an oil in 92% yield. Rf1, 0.65. Anal. Calcd. for C23H34N2O5 : C 66.00, H 9.19, N 6.69%. Found: C 65.58, H 8.28, N 7.13%.

Workup

  1. additionwas added slowly
  2. additionwas added
  3. stirringstirred for one hour
  4. extractionThe peptide was extracted into CHCl3
  5. washwashed with acid and base (0.5 N NaOH to remove HOBt)
  6. customon evaporating the solvent the product
  7. customwas obtained as an oil in 92% yield

Sources & evidence

ORD record
ord-1397fcaccb1546d1b928450fe3f865c1
Source dataset
uspto-grants-1988_11
Patent number
US04783523

Reaction notes

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