1,2-Dichloroethane → benzyl rel-(3R,4R)-3-(allyloxy)-4-[({[3-(trifluoromethyl)benzoyl]amino}acetyl)amino]pyrrolidine-1-carboxylate

HRID 564398Notes

Reaction equation

HRID 564398 reaction equation
[CH2:1]([O:4][C@H:5]1[C@H:9]([NH:10][C:11]([O:13]C(C)(C)C)=O)[CH2:8][N:7]([C:18]([O:20][CH2:21][C:22]2[CH:27]=[CH:26][CH:25]=[CH:24][CH:23]=2)=[O:19])[CH2:6]1)[CH:2]=[CH2:3].Cl.[F:29][C:30]([F:45])([F:44])[C:31]1[CH:32]=[C:33]([CH:41]=[CH:42][CH:43]=1)[C:34]([NH:36][CH2:37]C(O)=O)=[O:35].C(Cl)CCl.C1C=CC2N(O)N=NC=2C=1>CO>[CH2:1]([O:4][C@H:5]1[C@H:9]([NH:10][C:11](=[O:13])[CH2:37][NH:36][C:34](=[O:35])[C:33]2[CH:41]=[CH:42][CH:43]=[C:31]([C:30]([F:29])([F:45])[F:44])[CH:32]=2)[CH2:8][N:7]([C:18]([O:20][CH2:21][C:22]2[CH:23]=[CH:24][CH:25]=[CH:26][CH:27]=2)=[O:19])[CH2:6]1)[CH:2]=[CH2:3]

Participants

7

Reactant 5

HCID 111,2-DichloroethaneHCID 313Hydrochloric AcidHCID 757711-HydroxybenzotriazoleHCID 2777432((3-(Trifluoromethyl)benzoyl)amino)acetic acidHCID 59556149benzyl rel-(3R,4R)-3-(allyloxy)-4-[(tert-butoxycarbonyl)amino]pyrrolidine-1-carboxylate

Product 1

HCID 59556177benzyl rel-(3R,4R)-3-(allyloxy)-4-[({[3-(trifluoromethyl)benzoyl]amino}acetyl)amino]pyrrolidine-1-carboxylate

Reagents, catalysts & solvents 1

HCID 887MethanolSolvent

Procedure

To the solution of benzyl rel-(3R,4R)-3-(allyloxy)-4-[(tert-butoxycarbonyl)amino]pyrrolidine-1-carboxylate (200 mg, 0.53 mmol) in MeOH (5 mL) was added HCl (4.0 M in 1, 2 dioxane, 15 mL) dropwise. The reaction mixture was stirred at room temperature for 6 h, and the reaction mixture was concentrated under reduced pressure and the crude product was used in the following stop without further purification. The crude product was dissolved in DCM (5 mL). To this solution was added TEA (33.7 mg, 1.61 mmol), {[3-(trifluoromethyl)benzoyl]amino}acetic acid (200 mg, 0.81 mmol), EDC (205 mg, 1.07 mmol) and HOBt (145 mg, 1.07 mmol). The reaction mixture was stirred at room temperature overnight. The reaction was quenched by adding water (5 mL). The mixture was extracted with EtOAc (5 mL×3). The organic layers were combined, dried over MgSO4, filtered, concentrated under reduced pressure and subjected to column chromatography (EtOAc:hexanes, 1:3 to 1:1) to afford benzyl rel-(3R,4R)-3-(allyloxy)-4-[({[3-(trifluoromethyl)benzoyl]amino}acetyl)amino]pyrrolidine-1-carboxylate (222.5 mg (82%).

Workup

  1. concentrationthe reaction mixture was concentrated under reduced pressure
  2. customthe crude product was used in the following stop without further purification
  3. dissolutionThe crude product was dissolved in DCM (5 mL)
  4. stirringThe reaction mixture was stirred at room temperature overnight
  5. customThe reaction was quenched
  6. additionby adding water (5 mL)
  7. extractionThe mixture was extracted with EtOAc (5 mL×3)
  8. dry with materialdried over MgSO4
  9. filtrationfiltered
  10. concentrationconcentrated under reduced pressure

Sources & evidence

ORD record
ord-34a30f9aa23240529c2fd7e066424cd6
Source dataset
uspto-grants-2011_11
Patent number
US08067457B2

Reaction notes

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