Methanol → Ac-Ser-Asp-Ala-Ala-OH

HRID 1764783Notes

Reaction equation

HRID 1764783 reaction equation
[NH:1]([C:47]([CH3:49])=[O:48])[C@H:2]([C:12]([NH:14][C@H:15]([C:27]([NH:29][C@H:30]([C:32]([NH:34][C@H:35]([C:37]([O:39]CC1C=CC=CC=1)=[O:38])[CH3:36])=[O:33])[CH3:31])=[O:28])[CH2:16][C:17](=[O:26])[O:18]CC1C=CC=CC=1)=[O:13])[CH2:3][O:4]CC1C=CC=CC=1.CO.O>CC(O)=O>[NH:1]([C:47]([CH3:49])=[O:48])[C@H:2]([C:12]([NH:14][C@H:15]([C:27]([NH:29][C@H:30]([C:32]([NH:34][C@H:35]([C:37]([OH:39])=[O:38])[CH3:36])=[O:33])[CH3:31])=[O:28])[CH2:16][C:17](=[O:18])[OH:26])=[O:13])[CH2:3][OH:4]

Participants

5

Reactant 3

HCID 887MethanolHCID 962WaterHCID 131711274Ac-Ser(Bzl)-Asp(OBzl)-Ala-Ala-OBzl

Product 1

HCID 131711273Ac-Ser-Asp-Ala-Ala-OHYield 86.3%

Reagents, catalysts & solvents 1

HCID 176Acetic AcidSolvent

Procedure

Ac-Ser(Bzl)-Asp(OBzl)-Ala-Ala-OBzl (0.6 g, 0.888 mmol) was hydrogenated in a Parr apparatus at 50 psi in the presence of 0.62 g catalyst (5% Pd on BaSO4) in a solvent mixture consisting of 35 ml MeOH, 15 ml H2O, and 1 ml HOAc for 4 hours. The catalyst was filtered off and the filtrate concentrated to a smaller volume and lyophilized to give 0.38 g crude material. Tlc showed two minor contaminants in addition to the major component. The compound was then purified on a Bio-Rad AGl × 2 column (3 × 24 cm) which was washed with 0.2M NaOH, H2O, 0.2 M HOAc, and equilibrated with pH 8.5 buffer of 0.025 M ammonium acetate. The sample was applied at this pH and the column eluted with 250 ml each of the following acetic acid solution in the order of: 0.25M, 0.5M, 1.0M, 1.5M, 2.0M, 2.5M, 3.0M, 3.5M, 4.0M, and 4.5M. The flow rate was adjusted to approximately 50 ml/hr and each 10 ml fraction was collected into an LKB fraction collector. The compound was located by spotting a 5 μl portion from each tube on silica gel tlc plate (Merck 60, F-254) and developed in the solvent system of n-BuOH:HOAc:EtOAc:H2O (1:1:1:1) and then stained with chlorine-tolidine reaction. The fractions containing the major component were pooled and lyophilized twice to give 310 mg (86.3%) of the desired product; [α]D25 =-77.01° (c 1, 10% HOAc).

Workup

  1. filtrationThe catalyst was filtered off
  2. concentrationthe filtrate concentrated to a smaller volume
  3. customto give 0.38 g crude material
  4. additionin addition to the major component
  5. customThe compound was then purified on a Bio-Rad AGl × 2 column (3 × 24 cm) which
  6. washwas washed with 0.2M NaOH, H2O, 0.2 M HOAc
  7. washthe column eluted with 250 ml each of the following acetic acid solution in the order of: 0.25M, 0.5M, 1.0M, 1.5M, 2.0M, 2.5M, 3.0M, 3.5M, 4.0M, and 4.5M
  8. customeach 10 ml fraction was collected into an LKB fraction collector
  9. customstained with chlorine-tolidine reaction
  10. additionThe fractions containing the major component

Sources & evidence

ORD record
ord-a75d9f10a6aa427d9db526373051893f
Source dataset
uspto-grants-1978_09
Patent number
US04116951

Reaction notes

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