Ethyl bromoacetate → [3-(4',5'-Difluoro-2'-methoxy-biphenyl-4-yloxymethyl)-phenylamino]-acetic acid ethyl ester

HRID 547857Notizen

Reaktionsgleichung

Reaktionsgleichung von HRID 547857
[F:1][C:2]1[C:7]([F:8])=[CH:6][C:5]([C:9]2[CH:14]=[CH:13][C:12]([O:15][CH2:16][C:17]3[CH:18]=[C:19]([NH2:23])[CH:20]=[CH:21][CH:22]=3)=[CH:11][CH:10]=2)=[C:4]([O:24][CH3:25])[CH:3]=1.[CH2:26]([O:28][C:29](=[O:32])[CH2:30]Br)[CH3:27].C(=O)([O-])[O-].[K+].[K+]>C(#N)C>[CH2:26]([O:28][C:29](=[O:32])[CH2:30][NH:23][C:19]1[CH:20]=[CH:21][CH:22]=[C:17]([CH2:16][O:15][C:12]2[CH:11]=[CH:10][C:9]([C:5]3[CH:6]=[C:7]([F:8])[C:2]([F:1])=[CH:3][C:4]=3[O:24][CH3:25])=[CH:14][CH:13]=2)[CH:18]=1)[CH3:27]

Komponenten

5

Edukt 3

HCID 7748Ethyl bromoacetateHCID 11430Potassium CarbonateHCID 671537683-(4',5'-Difluoro-2'-methoxy-biphenyl-4-yloxymethyl)-phenylamine

Produkt 1

HCID 67153766[3-(4',5'-Difluoro-2'-methoxy-biphenyl-4-yloxymethyl)-phenylamino]-acetic acid ethyl esterAusbeute 44,5 %

Reagenzien, Katalysatoren, Lösungsmittel 1

HCID 6342AcetonitrileLösungsmittel2×

Reaktionsbedingungen

Temperatur
80 °C

Versuchsvorschrift

To a vial containing 3-(4′,5′-difluoro-2′-methoxy-biphenyl-4-yloxymethyl)-phenylamine (0.35 g, 1.0 mmol) dissolved in acetonitrile (1 mL) was added bromo-acetic acid ethyl ester (0.113 ml, 1.0 mmol) and potassium carbonate (167 mg, 1.2 mmol) and additional acetonitrile (5 mL). The vial was sealed and heated to 80° C. overnight. The reaction was partitioned between ethyl acetate (200 mL) and aqueous HCl (0.1 M, 200 mL). The organic layer was separated and the aqueous layer extracted with ethyl acetate (200 mL). The organic layers were washed with brine (100 mL), combined, dried over magnesium sulfate, concentrated, dissolved in a minimal amount of dichloromethane and purified by flash chromatography with a 0-30% ethyl acetate in hexanes gradient to yield [3-(4′,5′-difluoro-2′-methoxy-biphenyl-4-yloxymethyl)-phenylamino]-acetic acid ethyl ester as a clear semisolid (190 mg, 44%). LC-MS (ES) calculated for C24H23F2NO4, 427.16; found m/z 428 [M+H]+.

Aufarbeitung

  1. customThe vial was sealed
  2. customThe reaction was partitioned between ethyl acetate (200 mL) and aqueous HCl (0.1 M, 200 mL)
  3. customThe organic layer was separated
  4. extractionthe aqueous layer extracted with ethyl acetate (200 mL)
  5. washThe organic layers were washed with brine (100 mL)
  6. dry with materialdried over magnesium sulfate
  7. concentrationconcentrated
  8. dissolutiondissolved in a minimal amount of dichloromethane
  9. custompurified by flash chromatography with a 0-30% ethyl acetate in hexanes gradient

Quellen und Nachweise

ORD-Eintrag
ord-310d060f6f924a20bd02f6a635477d86
Quelldatensatz
uspto-grants-2011_05
Patentnummer
US07939569B1

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