Pivaloyl chloride → BOC-Val-MeLeu-Ala-Bzl

HRID 1583841Notes

Reaction equation

HRID 1583841 reaction equation
C(Cl)(=O)C(C)(C)C.C(N(C(C)C)C(C)C)C.[NH:17]([C:25]([O:27][C:28]([CH3:31])([CH3:30])[CH3:29])=[O:26])[C@H:18]([C:22]([OH:24])=O)[CH:19]([CH3:21])[CH3:20].[NH:32]([CH3:52])[C@H:33]([C:38]([NH:40][C@H:41]([C:43]([CH2:45][C:46]1[CH:51]=[CH:50][CH:49]=[CH:48][CH:47]=1)=[O:44])[CH3:42])=[O:39])[CH2:34][CH:35]([CH3:37])[CH3:36]>C(Cl)(Cl)Cl>[NH:17]([C:25]([O:27][C:28]([CH3:31])([CH3:30])[CH3:29])=[O:26])[C@H:18]([C:22]([N:32]([CH3:52])[C@H:33]([C:38]([NH:40][C@H:41]([C:43]([CH2:45][C:46]1[CH:51]=[CH:50][CH:49]=[CH:48][CH:47]=1)=[O:44])[CH3:42])=[O:39])[CH2:34][CH:35]([CH3:37])[CH3:36])=[O:24])[CH:19]([CH3:20])[CH3:21]

Participants

6

Reactant 4

HCID 62493Pivaloyl chlorideHCID 81531DiisopropylethylamineHCID 83693Boc-L-ValineHCID 131714435H-MeLeu-Ala-Bzl

Product 1

HCID 131714436BOC-Val-MeLeu-Ala-Bzl

Reagents, catalysts & solvents 1

HCID 6212ChloroformSolvent2×

Procedure

12.9 ml (12.7 g=106 mMol) pivaloyl chloride and 23 g (212 mMol) N-ethyl-diisopropylamine are added to a solution of 23.2 g (106 mMol) BOC-L-Val-OH in 400 ml chloroform and the mixture stirred for 2 hrs. at room temperature under a nitrogen atmosphere. 27.37 g (89 mMol) H-MeLeu-Ala-Bzl dissolved in 100 ml chloroform are then added and the reaction mixture stirred for a further 18 hrs. at 60° C. again under a nitrogen atmosphere. The obtained solution is washed with 300 ml 1N HCl, the aqueous phase extracted with 200 ml methylene chloride and the combined organic phases washed 2× with 200 ml saturated potassium carbonate solution. The aqueous phases are extracted with 200 ml methylene chloride, the combined organic phases dried over potassium carbonate, filtered and concentrated. The residue is chromatographed on 2 kg silica gel 60 (0.065-0.2 mm) with 1% methanol in methylene chloride as eluant to yield the title compound as a colourless oil: rotation [α]D25 =-97.2 (c=1.0 in chloroform).

Workup

  1. customat room temperature
  2. additionare then added
  3. stirringthe reaction mixture stirred for a further 18 hrs
  4. customat 60° C.
  5. washThe obtained solution is washed with 300 ml 1N HCl
  6. extractionthe aqueous phase extracted with 200 ml methylene chloride
  7. washthe combined organic phases washed 2× with 200 ml saturated potassium carbonate solution
  8. extractionThe aqueous phases are extracted with 200 ml methylene chloride
  9. dry with materialthe combined organic phases dried over potassium carbonate
  10. filtrationfiltered
  11. concentrationconcentrated
  12. customThe residue is chromatographed on 2 kg silica gel 60 (0.065-0.2 mm) with 1% methanol in methylene chloride as eluant

Sources & evidence

ORD record
ord-0095f10d82354713bc9fae0d17620017
Source dataset
uspto-grants-1985_11
Patent number
US04554351

Reaction notes

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