1,2-Dichloroethane → {4-Chloro-2-[2-(1-methyl-2-oxo-2-piperidin-1-yl-ethoxy)-benzyl]-phenoxy}-acetic acid methyl ester

HRID 2244477Notes

Reaction equation

HRID 2244477 reaction equation
C(Cl)CCl.[Cl:5][C:6]1[CH:7]=[CH:8][C:9]([O:25][CH2:26][C:27]([O:29][CH3:30])=[O:28])=[C:10]([CH:24]=1)[CH2:11][C:12]1[CH:23]=[CH:22][CH:21]=[CH:20][C:13]=1[O:14][CH:15]([CH3:19])[C:16](O)=[O:17].[CH:31]1[CH:36]=[N:35][C:34]2N(O)N=N[C:33]=2[CH:32]=1.N1CCCCC1.C(O)C(N)(CO)CO>CN(C=O)C>[CH3:30][O:29][C:27](=[O:28])[CH2:26][O:25][C:9]1[CH:8]=[CH:7][C:6]([Cl:5])=[CH:24][C:10]=1[CH2:11][C:12]1[CH:23]=[CH:22][CH:21]=[CH:20][C:13]=1[O:14][CH:15]([CH3:19])[C:16](=[O:17])[N:35]1[CH2:36][CH2:31][CH2:32][CH2:33][CH2:34]1

Participants

7

Reactant 5

HCID 111,2-DichloroethaneHCID 6503Tris(hydroxymethyl)aminomethaneHCID 8082PiperidineHCID 181649HOAtHCID 684527892-[2-(5-Chloro-2-methoxycarbonylmethoxy-benzyl)-phenoxy]-propionic acid2×

Product 1

HCID 68451410{4-Chloro-2-[2-(1-methyl-2-oxo-2-piperidin-1-yl-ethoxy)-benzyl]-phenoxy}-acetic acid methyl ester

Reagents, catalysts & solvents 1

HCID 6228DimethylformamideSolvent3×

Procedure

To a solution of PS-EDC (0.558 g, 1.42 mmol/g, 0.792 mmol) in DMF (2 mL) is added 2-[2-(5-chloro-2-methoxycarbonylmethoxy-benzyl)-phenoxy]-propionic acid (Intermediate B) (150 mg, 0.396 mmol) in DMF (2 mL) and HOAT (80.8 mg, 0.594 mmol) in DMF (2 mL). The reaction mixture is agitated for 50 minutes and then treated with piperidine (39.2 μL, 0.396 mmol) and agitated at RT for 2 days. Polymer supported trisamine (0.475 g, 1.42 mmol/g, 1.98 mmol) is then added and the mixture is further agitated overnight. The reaction mixture is filtered to remove the resins and rinsed with methanol and DCM. The filtrate is reduced in vacuo and the crude solid is re-dissolved in DCM and washed with water. The organic portion is separated using a phase separator and concentrated in vacuo to yield a solid which is purified by chromatography on silica eluting with EtOAc/iso-hexane (30% increasing to 50% EtOAc) to yield the titled product as a pale yellow oil; MH+=446.

Workup

  1. stirringagitated at RT for 2 days
  2. additionis then added
  3. stirringthe mixture is further agitated overnight
  4. filtrationThe reaction mixture is filtered
  5. customto remove the resins
  6. washrinsed with methanol and DCM
  7. dissolutionthe crude solid is re-dissolved in DCM
  8. washwashed with water
  9. customThe organic portion is separated
  10. concentrationconcentrated in vacuo
  11. customto yield a solid which
  12. customis purified by chromatography on silica eluting with EtOAc/iso-hexane (30% increasing to 50% EtOAc)

Sources & evidence

ORD record
ord-2ca07b5e266c4aaeaa017ca9bad82b87
Source dataset
uspto-grants-2010_03
Patent number
US07678826B2

Reaction notes

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