Acetic Acid → HCID 15631187, compound

HRID 1761422Notes

Reaction equation

HRID 1761422 reaction equation
C(OC([NH:11][C@@H:12]([C:31]([O:33]CC1C=CC=CC=1)=[O:32])[CH2:13][CH2:14][C:15]([N:17]1[C:25]2[C:20](=[CH:21][CH:22]=[CH:23][CH:24]=2)[CH2:19][C@H:18]1[C:26]([O:28][CH2:29][CH3:30])=[O:27])=[O:16])=O)C1C=CC=CC=1.C(O)(=O)C.C([O-])=O.[NH4+]>CO.O.[C].[Pd]>[NH2:11][C@@H:12]([C:31]([OH:33])=[O:32])[CH2:13][CH2:14][C:15]([N:17]1[C:25]2[C:20](=[CH:21][CH:22]=[CH:23][CH:24]=2)[CH2:19][C@H:18]1[C:26]([O:28][CH2:29][CH3:30])=[O:27])=[O:16]

Participants

7

Reactant 3

HCID 176Acetic AcidHCID 2723923Ammonium formateHCID 15631185HCID 15631185, compound

Product 1

HCID 15631187HCID 15631187, compoundYield 74.8%

Reagents, catalysts & solvents 3

HCID 178418390HCID 178418390, compoundCatalystHCID 887MethanolSolventHCID 962WaterSolvent

Conditions

Temperature
50 °C

Procedure

An aliquot (5.0 g) of this ester was suspended in a mixture of 100 ml of methanol and 30 ml of water, and 5 ml of acetic acid, 4.6 g of ammonium formate and 0.5 g of 10% palladium-carbon were added to the suspension. The mixture was stirred at 50° C. for 1 hour. The catalyst was removed by filtration. The mother liquor was adjusted to pH 7 and concentrated. The residual solution was cooled. The precipitated crystals were collected by filtration and recrystallized from ethanol/water (1/1) to give 2.2 g of ethyl 1-(gamma-D-glutamyl)indoline-2(S)-carboxylate (mp. 197°-200° C., decomp.). An aliquot (2.0 g) of this ester and 0.66 g of sodium carbonate were dissolved in 25 ml of water, and a solution of 3.3 g of N2 -benzyloxycarbonyl-N6 -t-butoxycarbonyl-L-lysine N-hydroxysuccinimide ester in 25 ml of THF was added. The mixture was stirred overnight at room temperature. Tetrahydrofuran was evaporated, and 5% aqueous potassium hydrogensulfate solution was added. The precipitated crystals were collected by filtration and recrystallized from ethanol/ether to give 3.3 g of ethyl 1-(N2 -benzyloxycarbonyl-N6 -t-butoxycarbonyl-L-lysyl-gamma-D-glutamyl)indoline-2(S)-carboxylate. An aliquot (0.7 g) of this ester was stirred with 10 ml of trifluoroacetic acid under ice cooling for 20 minutes. The reaction mixture was concentrated to dryness under reduced pressure, and the residue was subjected to CHP20P column chromatography (0%→50% acetonitrile/water gradient). Fractions containing the desired product were concentrated, and the precipitated crystals were collected by filtration to give 0.34 g of the captioned compound.

Workup

  1. additionwere added to the suspension
  2. customThe catalyst was removed by filtration
  3. concentrationconcentrated
  4. temperatureThe residual solution was cooled
  5. filtrationThe precipitated crystals were collected by filtration
  6. customrecrystallized from ethanol/water (1/1)

Sources & evidence

ORD record
ord-234c824228c04b30a8c66f7135edb699
Source dataset
uspto-grants-1989_05
Patent number
US04826814

Reaction notes

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