Water → (S)-tert-butyl 2-((2-(4-bromophenyl)-2-oxoethyl)carbamoyl)pyrrolidine-1-carboxylate

HRID 1963972Notes

Reaction equation

HRID 1963972 reaction equation
[C:1]([N:8]1[CH2:15][CH2:14][CH2:13][C@H:9]1[C:10]([OH:12])=O)([O:3][C:4]([CH3:7])([CH3:6])[CH3:5])=[O:2].C1C=CC2N(O)N=NC=2C=1.O.Cl.C(N=C=NCCCN(C)C)C.Cl.[NH2:40][CH2:41][C:42]([C:44]1[CH:49]=[CH:48][C:47]([Br:50])=[CH:46][CH:45]=1)=[O:43].C(N(CC)C(C)C)(C)C>ClCCl>[Br:50][C:47]1[CH:46]=[CH:45][C:44]([C:42](=[O:43])[CH2:41][NH:40][C:10]([C@@H:9]2[CH2:13][CH2:14][CH2:15][N:8]2[C:1]([O:3][C:4]([CH3:5])([CH3:6])[CH3:7])=[O:2])=[O:12])=[CH:49][CH:48]=1

Participants

8

Reactant 6

HCID 962WaterHCID 757711-HydroxybenzotriazoleHCID 81531DiisopropylethylamineHCID 850831,2-Pyrrolidinedicarboxylic acid, 1-(1,1-dimethylethyl) ester, (2S)-HCID 27239391,3-Propanediamine, N'-(ethylcarbonimidoyl)-N,N-dimethyl-, monohydrochlorideHCID 27982162-Amino-1-(4-bromophenyl)ethan-1-one hydrochloride

Product 1

HCID 56605334(S)-tert-butyl 2-((2-(4-bromophenyl)-2-oxoethyl)carbamoyl)pyrrolidine-1-carboxylateYield 90%

Reagents, catalysts & solvents 1

HCID 6344DichloromethaneSolvent

Procedure

A solution of N-Boc-L-Proline (5.16 g, 24.0 mmol) and HOBt.H2O (3.67 g, 24.0 mmol) was stirred at room temperature for 10 min and then treated with N-ethyl-N′-(3-dimethylaminopropyl) carbodiimide hydrochloride (EDC.HCl, 4.60 g, 24.0 mmol). The resulting mixture was stirred at room temperature for 30 min and then treated with a yellow solution formed by stirring 2-amino-4′-bromoacetophenone hydrochloride (5.0 g, 20.0 mmol) and N,N-diisopropylethylamine (DIPEA, 2.58 g, 20 mmol) in dichloromethane (DCM, 150 ml) at room temperature for 10 min. The resulting mixture was stirred at room temperature overnight and then filtered through Celite® to remove the precipitate. The filtrate was extracted with DCM and H2O. The organic layer was washed with brine, dried over MgSO4, filtered, and concentrated. The residue was purified with column chromatography (ethyl acetate:hexanes=2:5) to yield pure product 1a as a yellow gel (7.39 g, 90%).

Workup

  1. additiontreated with a yellow solution
  2. customformed
  3. stirringThe resulting mixture was stirred at room temperature overnight
  4. filtrationfiltered through Celite®
  5. customto remove the precipitate
  6. extractionThe filtrate was extracted with DCM and H2O
  7. washThe organic layer was washed with brine
  8. dry with materialdried over MgSO4
  9. filtrationfiltered
  10. concentrationconcentrated
  11. customThe residue was purified with column chromatography (ethyl acetate:hexanes=2:5)

Sources & evidence

ORD record
ord-130b6e45d6a948a8af6d28eb49552e73
Source dataset
uspto-grants-2013_04
Patent number
US08415482B2

Reaction notes

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