Ethylmorpholine → N-[(2-chloro-4-fluorophenyl)methyl]-1-ethyl-5-oxo-D-prolinamide

HRID 554107Notes

Reaction equation

HRID 554107 reaction equation
[CH2:1]([N:3]1[C:10](=[O:11])[CH2:9][CH2:8][C@H:4]1[C:5]([OH:7])=O)[CH3:2].Cl.CN(C)CCCN=C=NCC.ON1C2C=CC=CC=2N=N1.C(N1CCOCC1)C.[Cl:42][C:43]1[CH:50]=[C:49]([F:51])[CH:48]=[CH:47][C:44]=1[CH2:45][NH2:46].C(=O)([O-])O.[Na+]>ClCCl.CN(C)C=O>[Cl:42][C:43]1[CH:50]=[C:49]([F:51])[CH:48]=[CH:47][C:44]=1[CH2:45][NH:46][C:5](=[O:7])[C@H:4]1[CH2:8][CH2:9][C:10](=[O:11])[N:3]1[CH2:1][CH3:2]

Participants

9

Reactant 6

HCID 7525EthylmorpholineHCID 757711-HydroxybenzotriazoleHCID 1399092-Chloro-4-fluorobenzylamineHCID 516892Sodium BicarbonateHCID 27239391,3-Propanediamine, N'-(ethylcarbonimidoyl)-N,N-dimethyl-, monohydrochlorideHCID 18605196L-Proline, 1-ethyl-5-oxo-

Product 1

HCID 49865054N-[(2-chloro-4-fluorophenyl)methyl]-1-ethyl-5-oxo-D-prolinamide

Reagents, catalysts & solvents 2

HCID 6228DimethylformamideSolventHCID 6344DichloromethaneSolvent

Procedure

1-ethyl-5-oxoproline (0.100 g, 0.64 mmol) was dissolved in a mixture of dichloromethane (3 ml) and dimethylformamide (0.5 ml) and to this was added N-(3-dimethylaminopropyl)-N′-ethylcarbodiimide hydrochloride (0.147 g, 0.77 mmol), 1-hydroxybenzotriazole (0.104 g, 0.77 mmol), and N-ethyl morpholine (0.244 ml, 1.92 mmol). The mixture was stirred for 10 minutes and then 2-chloro-4-fluorobenzylamine was added to the mixture and stirring continued overnight (˜16 hrs) at room temperature. The mixture was then treated with saturated aqueous sodium hydrogen carbonate (˜2 ml) and stirred vigorously for ˜10 minutes. The aqueous layer was removed using a phase separator and extracted with more dichloromethane (2×1 ml). The combined organic layers were concentrated to give a yellow oil and this was subsequently purified by mass-directed automated HPLC to give N-[(2-chloro-4-fluorophenyl)methyl]-1-ethyl-5-oxo-D-prolinamide (0.065 g) as a white solid. LC/MS [M+H]+=299, retention time=2.16 minutes.

Workup

  1. stirringstirring continued overnight (˜16 hrs) at room temperature
  2. stirringstirred vigorously for ˜10 minutes
  3. customThe aqueous layer was removed
  4. extractionextracted with more dichloromethane (2×1 ml)
  5. concentrationThe combined organic layers were concentrated
  6. customto give a yellow oil
  7. customthis was subsequently purified

Sources & evidence

ORD record
ord-a22223d4f7d443a8a7d23fd77d71951d
Source dataset
uspto-grants-2011_11
Patent number
US08048907B2

Reaction notes

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