Ethylmorpholine → HCID 67461554, compound

HRID 554088Notes

Reaction equation

HRID 554088 reaction equation
[CH2:1]([N:3]1[C:10](=[O:11])[CH:9]([CH2:12][C:13]2[CH:18]=[CH:17][CH:16]=[CH:15][CH:14]=2)[CH2:8][C@H:4]1[C:5]([OH:7])=O)[CH3:2].C(N1CCOCC1)C.ON1C2C=CC=CC=2N=N1.Cl.CN(C)CCCN=C=NCC.[Cl:49][C:50]1[CH:55]=[C:54]([F:56])[CH:53]=[CH:52][C:51]=1[CH2:57][NH2:58].C(=O)([O-])O.[Na+]>ClCCl.CN(C)C=O>[Cl:49][C:50]1[CH:55]=[C:54]([F:56])[CH:53]=[CH:52][C:51]=1[CH2:57][NH:58][C:5](=[O:7])[C@@H:4]1[CH2:8][CH:9]([CH2:12][C:13]2[CH:18]=[CH:17][CH:16]=[CH:15][CH:14]=2)[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 67459915HCID 67459915, compound

Product 1

HCID 67461554HCID 67461554, compoundYield 11.4%

Reagents, catalysts & solvents 2

HCID 6228DimethylformamideSolventHCID 6344DichloromethaneSolvent

Procedure

Crude 1-ethyl-5-oxo-4-(phenylmethyl)-proline (0.052 g, 0.09 mmol, prepared as described below) was suspended in a mixture of dichloromethane (0.5 ml) and dimethylformamide (0.5 ml) and to this was added N-ethyl morpholine (0.034 ml, 0.27 mmol) causing most of the material to dissolve. 1-Hydroxybenzotriazole (0.016 g, 0.12 mmol) and N-(3-dimethylaminopropyl)-N′-ethylcarbodiimide hydrochloride (0.022 g, 0.12 mmol) were then added and the mixture was stirred for 10 minutes before adding [(2-chloro-4-fluorophenyl)methyl]amine (0.019 g, 0.12 mmol). The mixture was then left to stand at room temperature overnight. Saturated aqueous sodium hydrogen carbonate (˜2 ml) was added to the mixture and stirred for 10 minutes. The organic layer was isolated by filtering through a phase separator and then washed with 2M aqueous hydrogen chloride. The organic layer was separated again and evaporated to give a yellow oil which was purified by mass-directed automated HPLC to give pure N-[(2-chloro-4-fluorophenyl)methyl]-1-ethyl-5-oxo-4-(phenylmethyl)-prolinamide (0.004 g) as a colourless oil. LC/MS [M+H]+=389, retention time=2.90 minutes.

Workup

  1. dissolutionto dissolve
  2. waitThe mixture was then left
  3. waitto stand at room temperature overnight
  4. stirringstirred for 10 minutes
  5. customThe organic layer was isolated
  6. filtrationby filtering through a phase separator
  7. washwashed with 2M aqueous hydrogen chloride
  8. customThe organic layer was separated again
  9. customevaporated
  10. customto give a yellow oil which
  11. customwas purified

Sources & evidence

ORD record
ord-fbe6a27f059f4378b3c1622d09b54a98
Source dataset
uspto-grants-2011_11
Patent number
US08048907B2

Reaction notes

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