Hydrochloric Acid → HCID 21100012, compound

HRID 1352190Notes

Reaction equation

HRID 1352190 reaction equation
[NH2:1][C:2]1[CH:7]=[CH:6][C:5]([CH2:8][C:9]([OH:11])=[O:10])=[CH:4][CH:3]=1.[OH-].[Na+].[CH2:14]([O:21][C:22](Cl)=[O:23])[C:15]1[CH:20]=[CH:19][CH:18]=[CH:17][CH:16]=1.Cl.[C:26]1(=[O:32])[NH:30][C:29](=[O:31])[CH2:28][CH2:27]1.ON1C(=O)CCC1=O.C1(N=C=NC2CCCCC2)CCCCC1>C1COCC1.O1CCOCC1.O>[CH2:14]([O:21][C:22]([NH:1][C:2]1[CH:3]=[CH:4][C:5]([CH2:8][C:9]([O:11][N:30]2[C:26](=[O:32])[CH2:27][CH2:28][C:29]2=[O:31])=[O:10])=[CH:6][CH:7]=1)=[O:23])[C:15]1[CH:20]=[CH:19][CH:18]=[CH:17][CH:16]=1

Participants

10

Reactant 7

HCID 313Hydrochloric AcidHCID 10387Benzyl chloroformateHCID 10868DicyclohexylcarbodiimideHCID 11439SuccinimideHCID 145334-Aminophenylacetic acidHCID 14798Sodium HydroxideHCID 80170N-Hydroxysuccinimide

Product 1

HCID 21100012HCID 21100012, compound

Reagents, catalysts & solvents 2

HCID 8028TetrahydrofuranSolventHCID 218864351,4-Dioxane--water (1/1)Solvent

Procedure

To an ice-cold solution of 4-aminophenylacetic acid (500 mg, 3.307 mmol) in 1:1 dioxane-water (10 mL) was added a solution of 2 N NaOH (˜2.2 equivalent, pH 9–10). This mixture was treated with benzylchloroformate (0.5 mL, 3.681 mmol) and the solution was allowed to stir in an ice-bath for 2 h. The reaction mixture was acidified with an aqueous solution of 1 N HCl (pH ˜4), extracted with ethyl acetate, dried (Na2SO4), and concentrated in vacuo to give a solid as crude product. Purification of the solid (SiO2, 10:1 CHCl3/MeOH) gave N-Cbz protected phenylacetic acid (856 mg, 91%) as a pure white solid. To make the succinimide active ester, a mixture of N-Cbz protected acid (120 mg, 0.421 mmol), N-hydroxysuccinimide (53 mg 97%, 0.445 mmol), and dicyclohexylcarbodiimide (88 mg, 0.421 mmol) in dry THF (4 mL) was stirred at room temperature under an atmosphere of argon for 2 h. This solution was directly used for preparation of compound 35.

Workup

  1. extractionextracted with ethyl acetate
  2. dry with materialdried (Na2SO4)
  3. concentrationconcentrated in vacuo
  4. customto give a solid as crude product
  5. customPurification of the solid (SiO2, 10:1 CHCl3/MeOH)
  6. customgave N-Cbz protected phenylacetic acid (856 mg, 91%) as a pure white solid
  7. stirringwas stirred at room temperature under an atmosphere of argon for 2 h

Sources & evidence

ORD record
ord-0fd4db795cf0450cac239ce864ff3ab0
Source dataset
uspto-grants-2007_05
Patent number
US07220727B2

Reaction notes

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