Hydrochloric Acid → ((2S,4R)-4-amino-1-(2-chlorobenzylcarbamoyl)pyrrolidin-2-yl)methyl 4-ethylphenylcarbamate

HRID 655980

Reaction equation

HRID 655980 reaction equation
C1C2C(COC([NH:18][C@H:19]3[CH2:23][N:22]([C:24]([O:26]C(C)(C)C)=O)[C@H:21]([CH2:31][O:32][C:33](=[O:43])[NH:34][C:35]4[CH:40]=[CH:39][C:38]([CH2:41][CH3:42])=[CH:37][CH:36]=4)[CH2:20]3)=O)C3C(=CC=CC=3)C=2C=CC=1.Cl.CCN(C(C)C)C(C)C.[Cl:54][C:55]1[CH:64]=[CH:63][CH:62]=[CH:61][C:56]=1[CH2:57][N:58]=C=O>CO>[CH2:41]([C:38]1[CH:37]=[CH:36][C:35]([NH:34][C:33](=[O:43])[O:32][CH2:31][C@@H:21]2[CH2:20][C@@H:19]([NH2:18])[CH2:23][N:22]2[C:24](=[O:26])[NH:58][CH2:57][C:56]2[CH:61]=[CH:62][CH:63]=[CH:64][C:55]=2[Cl:54])=[CH:40][CH:39]=1)[CH3:42]

Participants

6

Reactant 4

HCID 313Hydrochloric AcidHCID 81531DiisopropylethylamineHCID 27333671-Chloro-2-(isocyanatomethyl)benzeneHCID 59778440(2S,4R)-tert-butyl 4-(((9H-fluoren-9-yl)methoxy)carbonylamino)-2-((4-ethylphenylcarbamoyloxy)methyl)pyrrolidine-1-carboxylate

Product 1

HCID 59778486((2S,4R)-4-amino-1-(2-chlorobenzylcarbamoyl)pyrrolidin-2-yl)methyl 4-ethylphenylcarbamateYield 53%

Reagents, catalysts & solvents 1

HCID 887MethanolSolvent

Procedure

To a solution of crude (2S,4R)-tert-butyl 4-(((9H-fluoren-9-yl)methoxy)carbonylamino)-2-((4-ethylphenylcarbamoyloxy)methyl)pyrrolidine-1-carboxylate in MeOH was added HCl (4 N in dioxane). The reaction was stirred at rt for 1 h and concentrated. The residue was dissolved in THF (10 mL). To this solution were added DIEA (469 μL, 2.7 mmol) and 2-chlorobenzylisocyanate. The mixture was stirred at rt for 1 h and concentrated. The residue was dissolved in 10 ml of 20% piperidine in DCM. The reaction mixture was stirred at rt for 15 min, concentrated and purified on RP-HPLC using a mixture of acetonitrile and H2O to give ((2S,4R)-4-amino-1-(2-chlorobenzylcarbamoyl)pyrrolidin-2-yl)methyl 4-ethylphenylcarbamate (210 mg, 53% for 4 steps). LRMS (M+H+) m/z 431.1.

Workup

  1. concentrationconcentrated
  2. dissolutionThe residue was dissolved in THF (10 mL)
  3. stirringThe mixture was stirred at rt for 1 h
  4. concentrationconcentrated
  5. dissolutionThe residue was dissolved in 10 ml of 20% piperidine in DCM
  6. stirringThe reaction mixture was stirred at rt for 15 min
  7. concentrationconcentrated
  8. custompurified on RP-HPLC
  9. additiona mixture of acetonitrile and H2O

Sources & evidence

ORD record
ord-3f6d90b2606341d6b860fe47cb44386e
Source dataset
uspto-grants-2011_12
Patent number
US08071625B2

Linked notes

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