Citric Acid → HCID 11235137, compound

HRID 565087Notes

Reaction equation

HRID 565087 reaction equation
[NH2-].[Na+].C([O:10][C:11](=O)[C@H:12]([CH2:28][C:29]1[CH:34]=[CH:33][CH:32]=[CH:31][CH:30]=1)[N:13]([CH2:21][C:22]1[CH:27]=[CH:26][CH:25]=[CH:24][CH:23]=1)[CH2:14][C:15]1[CH:20]=[CH:19][CH:18]=[CH:17][CH:16]=1)C1C=CC=CC=1.C(O)(=O)CC(CC(O)=O)(C(O)=O)O.C(OCC)(=O)C.[CH3:55][S:56]([CH3:58])=[O:57]>O1CCCC1>[CH2:14]([N:13]([C@@H:12]([CH2:28][C:29]1[CH:30]=[CH:31][CH:32]=[CH:33][CH:34]=1)[C:11](=[O:10])[CH2:55][S:56]([CH3:58])=[O:57])[CH2:21][C:22]1[CH:23]=[CH:24][CH:25]=[CH:26][CH:27]=1)[C:15]1[CH:16]=[CH:17][CH:18]=[CH:19][CH:20]=1

Participants

7

Reactant 5

HCID 311Citric AcidHCID 679Dimethyl SulfoxideHCID 8857Ethyl AcetateHCID 24533Sodium amideHCID 10928230Benzyl N,N-dibenzyl-L-phenylalaninate

Product 1

HCID 11235137HCID 11235137, compoundYield 85.6%

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent2×

Conditions

Temperature
74.5 °C

Procedure

3.76 g (96.39 mmol) of sodium amide was suspended in 40 ml of dimethylsulfoxide and heated at from 74 to 75° C. for 30 minutes. 40 ml of tetrahydrofuran was added to the resulting solution and cooled to 0° C. To this was dropwise added a solution of 15.47 g (90.5 wt. %, 32.14 mmol) of N,N-dibenzyl-(L)-phenylalanine benzyl ester as dissolved in 20 ml of tetrahydrofuran, while keeping it at 0° C. After these were reacted at 0° C. for 30 minutes, 120 ml of an aqueous solution of 10% citric acid and 100 ml of ethyl acetate were added to the reaction mixture, which was thus subjected to phase separation. The aqueous layer thus separated was extracted once with 50 ml of ethyl acetate, and the resulting extract was combined with the previously-separated organic layer and then washed with 60 ml of a saturated saline solution. This was dried with anhydrous sodium sulfate, filtered and concentrated, and the resulting residue was purified through silica gel column chromatography (hexane/ethyl acetate=from 2/1 to 1/3) and then crystallized in toluene/hexane to obtain 11.16 g of the above-entitled compound. The yield was 85.6%. The integral ratio in 1H-NMR of the compound verified that the ratio of the diastereomers constituting it is about 1:1.

Workup

  1. temperaturecooled to 0° C
  2. customat 0° C
  3. customAfter these were reacted at 0° C. for 30 minutes
  4. customwas thus subjected to phase separation
  5. customThe aqueous layer thus separated
  6. extractionwas extracted once with 50 ml of ethyl acetate
  7. extractionthe resulting extract
  8. washwashed with 60 ml of a saturated saline solution
  9. dry with materialThis was dried with anhydrous sodium sulfate
  10. filtrationfiltered
  11. concentrationconcentrated
  12. customthe resulting residue was purified through silica gel column chromatography (hexane/ethyl acetate=from 2/1 to 1/3)
  13. customcrystallized in toluene/hexane

Sources & evidence

ORD record
ord-a0c9ac4c482848f686b34ed7672ea8e1
Source dataset
uspto-grants-2001_01
Patent number
US06169200A

Reaction notes

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