1,2-Dichloroethane → HCID 19705517, compound

HRID 727578Notes

Reaction equation

HRID 727578 reaction equation
[F:1][C:2]1[CH:3]=[C:4]([CH:32]=[CH:33][C:34]=1[F:35])[C:5]([NH:7][CH2:8][CH2:9][CH:10]([C:14]1([CH2:28][CH2:29][CH2:30][OH:31])[CH2:18][CH2:17][N:16]([CH2:19][CH2:20][C:21]2[CH:26]=[CH:25][CH:24]=[CH:23][CH:22]=2)[C:15]1=[O:27])[C:11]([OH:13])=O)=[O:6].C1C=CC2N(O)N=NC=2C=1.C(Cl)CCl.CN1CCOCC1.Cl.[CH2:58]([O:65][NH2:66])[C:59]1[CH:64]=[CH:63][CH:62]=[CH:61][CH:60]=1>O.CCOC(C)=O.C(Cl)Cl.CN(C=O)C>[F:1][C:2]1[CH:3]=[C:4]([CH:32]=[CH:33][C:34]=1[F:35])[C:5]([NH:7][CH2:8][CH2:9][CH:10]([C:14]1([CH2:28][CH2:29][CH2:30][OH:31])[CH2:18][CH2:17][N:16]([CH2:19][CH2:20][C:21]2[CH:26]=[CH:25][CH:24]=[CH:23][CH:22]=2)[C:15]1=[O:27])[C:11]([NH:66][O:65][CH2:58][C:59]1[CH:64]=[CH:63][CH:62]=[CH:61][CH:60]=1)=[O:13])=[O:6]

Participants

9

Reactant 5

HCID 111,2-DichloroethaneHCID 79724-Methylmorpholine2×HCID 757711-HydroxybenzotriazoleHCID 102312Benzyloxyamine hydrochlorideHCID 19705436HCID 19705436, compound

Product 1

HCID 19705517HCID 19705517, compoundYield 84.6%

Reagents, catalysts & solvents 3

HCID 962WaterSolventHCID 8857Ethyl AcetateSolventHCID 22350042dichloromethane N,N-dimethylformamideSolvent

Procedure

A cold (0° C.) solution of α-[2-[(3,4-difluorobenzoyl)amino]ethyl]-3-(3-hydroxypropyl)-2-oxo-1-(2-phenylethyl)-3-pyrrolidineacetic acid (586 mg, 1.20 mmol) in 2:1 CH2Cl2 /DMF (7.5 mL) is treated with HOBT (195 mg, 1.44 mmol), EDC (276 mg, 1.44 mmol), and 4-methylmorpholine (158 μL, 1.44 mmol). The ice bath is removed, and after 1 hour, O-benzylhydroxylamine HCl (287 mg, 1.80 mmol) and a second portion of 4-methylmorpholine (198 μL, 1.80 mmol) are added. The solution is stirred overnight at room temperature under N2. The solution is diluted with H2O (25 mL) and extracted into CH2Cl2 (3×50 mL). The extracts are combined, dried over anhydrous MgSO4, filtered, and concentrated under reduced pressure to provide an oil. The residual oil is reconstituted in EtOAc (50 mL) and washed with 1N HCl (10 mL), 1N NaOH (10 mL), H2O (10 mL), and brine (10 mL). The organic layer is dried over anhydrous MgSO4, filtered, and concentrated under reduced pressure to give 603 mg of a white foam. The material is purified by silica gel chromatography (25 g SG; EtOAc) to provide 433 mg (62%) of the title compound as a white, amorphous solid:

Workup

  1. customThe ice bath is removed
  2. extractionextracted into CH2Cl2 (3×50 mL)
  3. dry with materialdried over anhydrous MgSO4
  4. filtrationfiltered
  5. concentrationconcentrated under reduced pressure
  6. customto provide an oil
  7. washwashed with 1N HCl (10 mL), 1N NaOH (10 mL), H2O (10 mL), and brine (10 mL)
  8. dry with materialThe organic layer is dried over anhydrous MgSO4
  9. filtrationfiltered
  10. concentrationconcentrated under reduced pressure

Sources & evidence

ORD record
ord-96373988442e4038a54c94e8f7d1dde4
Source dataset
uspto-grants-1998_01
Patent number
US05712300

Reaction notes

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