1,2-Dichloroethane → HCID 19705519, compound

HRID 727549Notes

Reaction equation

HRID 727549 reaction equation
[O:1]=[C:2]1[C:10]2[C:5](=[CH:6][CH:7]=[CH:8][CH:9]=2)[C:4](=[O:11])[N:3]1[CH2:12][CH2:13][CH:14]([C:18]1([CH2:31][CH:32]([CH3:34])[CH3:33])[CH2:22][CH2:21][N:20]([CH2:23][C:24]2[CH:29]=[CH:28][CH:27]=[CH:26][CH:25]=2)[C:19]1=[O:30])[C:15](O)=[O:16].[OH:35][N:36]1C2C=CC=CC=2N=N1.C(Cl)CCl.CN1CCOCC1.Cl.NO>ClCl.CN(C=O)C.O>[O:11]=[C:4]1[C:5]2[C:10](=[CH:9][CH:8]=[CH:7][CH:6]=2)[C:2](=[O:1])[N:3]1[CH2:12][CH2:13][CH:14]([C:18]1([CH2:31][CH:32]([CH3:33])[CH3:34])[CH2:22][CH2:21][N:20]([CH2:23][C:24]2[CH:29]=[CH:28][CH:27]=[CH:26][CH:25]=2)[C:19]1=[O:30])[C:15]([NH:36][OH:35])=[O:16]

Participants

8

Reactant 5

HCID 111,2-DichloroethaneHCID 79724-MethylmorpholineHCID 757711-HydroxybenzotriazoleHCID 443297Hydroxyamine hydrochlorideHCID 19705502HCID 19705502, compound

Product 1

HCID 19705519HCID 19705519, compoundYield 74.5%

Reagents, catalysts & solvents 2

HCID 962WaterSolventHCID 86751989HCID 86751989, compoundSolvent

Procedure

A cold (0° C.) solution of α-[2-(1,3-dihydro-1,3-dioxo-2H-isoindol-2-yl)ethyl]-3-(2-methylpropyl)-2-oxo-1-(phenylmethyl)-3-pyrrolidineacetic acid (559 mg) in CH2 Cl2 /DMF (8 mL/2 mL) is treated with 1-hydroxybenzotriazole (158 mg, 1.17 mmol), 4-methyknorpholine (129 μL, 1.17 mmol), and EDC (224 mg, 1.17 mmol). After 1 hour, additional 4-methylmorpholine (159 μL, 1.45 mmol) and hydroxylamine HCl (101 mg, 1.45 mmol) are added. The solution is allowed to slowly warm to room temperature, stirring under N2 overnight. The reaction mixture is diluted with H2O (25 mL) and extracted into CH2Cl2 (3×50 mL). The organic extracts are dried over anhydrous Na2SO4, filtered, concentrated under reduced pressure, and reconstituted in EtOAc (50 mL). The EtOAc layer is washed with more H2O (3×25 mL) and brine (25 mL). The organic layer is dried over anhydrous Na2SO4, filtered, and concentrated under reduced pressure to give 416 mg of white foam. The foam is purified by silica gel chromatography (50 g SG, 2% MeOH/CHCl3) to yield 220 mg of white foam which is triturated with Et2O to give 181 mg (39%) of the title compound as a white solid (mp 162°-164° C.).

Workup

  1. extractionextracted into CH2Cl2 (3×50 mL)
  2. dry with materialThe organic extracts are dried over anhydrous Na2SO4
  3. filtrationfiltered
  4. concentrationconcentrated under reduced pressure
  5. washThe EtOAc layer is washed with more H2O (3×25 mL) and brine (25 mL)
  6. dry with materialThe organic layer is dried over anhydrous Na2SO4
  7. filtrationfiltered
  8. concentrationconcentrated under reduced pressure

Sources & evidence

ORD record
ord-c89a2dc678aa411aa3b11dbe52c3a38d
Source dataset
uspto-grants-1998_01
Patent number
US05712300

Reaction notes

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