(+/-)-2-bromo-4-(5-chloro-2-ethoxycarbonylmethoxy-phenyl)-6,7-dihydro-4H-thiazolo[5,4-c]pyridine-5-carboxylic acid benzyl ester → (+/-)-4-(2-Carboxymethoxy-5-chloro-phenyl)-2-propyl-6,7-dihydro-4H-thiazolo[5,4-c]pyridine-5-carboxylic acid benzyl ester

HRID 1754834Notizen

Reaktionsgleichung

Reaktionsgleichung von HRID 1754834
[CH2:1]([O:8][C:9]([N:11]1[CH2:16][CH2:15][C:14]2[N:17]=[C:18](Br)[S:19][C:13]=2[CH:12]1[C:21]1[CH:26]=[C:25]([Cl:27])[CH:24]=[CH:23][C:22]=1[O:28][CH2:29][C:30]([O:32]CC)=[O:31])=[O:10])[C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][CH:3]=1.[Br-].[CH2:36]([Zn+])[CH2:37][CH3:38]>C1COCC1.[Pd].C1(P(C2C=CC=CC=2)C2C=CC=CC=2)C=CC=CC=1.C1(P(C2C=CC=CC=2)C2C=CC=CC=2)C=CC=CC=1.C1(P(C2C=CC=CC=2)C2C=CC=CC=2)C=CC=CC=1.C1(P(C2C=CC=CC=2)C2C=CC=CC=2)C=CC=CC=1>[CH2:1]([O:8][C:9]([N:11]1[CH2:16][CH2:15][C:14]2[N:17]=[C:18]([CH2:36][CH2:37][CH3:38])[S:19][C:13]=2[CH:12]1[C:21]1[CH:26]=[C:25]([Cl:27])[CH:24]=[CH:23][C:22]=1[O:28][CH2:29][C:30]([OH:32])=[O:31])=[O:10])[C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][CH:3]=1

Komponenten

5

Edukt 2

HCID 90022152(+/-)-2-bromo-4-(5-chloro-2-ethoxycarbonylmethoxy-phenyl)-6,7-dihydro-4H-thiazolo[5,4-c]pyridine-5-carboxylic acid benzyl esterHCID 178455869HCID 178455869, Verbindung

Produkt 1

HCID 72948701(+/-)-4-(2-Carboxymethoxy-5-chloro-phenyl)-2-propyl-6,7-dihydro-4H-thiazolo[5,4-c]pyridine-5-carboxylic acid benzyl ester

Reagenzien, Katalysatoren, Lösungsmittel 2

HCID 11979704Tetrakis(triphenylphosphine)palladiumKatalysatorHCID 8028TetrahydrofuranLösungsmittel2×

Reaktionsbedingungen

Temperatur
50 °C

Versuchsvorschrift

To a solution under N2 of (±)-2-bromo-4-(5-chloro-2-ethoxycarbonylmethoxy-phenyl)-6,7-dihydro-4H-thiazolo[5,4-c]pyridine-5-carboxylic acid benzyl ester (50 mg, 0.09 mmol, 1.00 eq.) and 0.5M propylzinc bromide in THF (0.36 mL, 0.18 mmol, 2.00 eq.) in THF (10 mL), tetrakis(triphenylphosphine) palladium (0) (5.1 mg, 4 μmol, 0.05 eq) was added. The mixture was stirred at 50° C. for 18 hours. The mixture was allowed to cool to r.t. and concentrated in vacuo. The residue was taken up in DMF, filtered, and purified by prep. HPLC (column: Atlantis, 30×75 mm, 10 um, UV/MS, acidic conditions) and concentrated in vacuo. The resulting ester was dissolved in DMF (0.5 mL), 1M aq. NaOH soln. (0.5 mL) was added. The resulting solution was stirred at r.t. for 18 hours. The solution was neutralized with formic acid (1 mL), filtered, and then purified by prep. HPLC (column: Atlantis, 30×75 mm, 10 um, UV/MS, acidic conditions) and concentrated in vacuo to give the desired acid as a white solid.

Aufarbeitung

  1. temperatureto cool to r.t.
  2. concentrationconcentrated in vacuo
  3. filtrationfiltered
  4. custompurified by prep
  5. concentrationHPLC (column: Atlantis, 30×75 mm, 10 um, UV/MS, acidic conditions) and concentrated in vacuo
  6. dissolutionThe resulting ester was dissolved in DMF (0.5 mL)
  7. addition(0.5 mL) was added
  8. stirringThe resulting solution was stirred at r.t. for 18 hours
  9. filtrationfiltered
  10. custompurified by prep
  11. concentrationHPLC (column: Atlantis, 30×75 mm, 10 um, UV/MS, acidic conditions) and concentrated in vacuo

Quellen und Nachweise

ORD-Eintrag
ord-392de0f21e0d41f09d767a4ad9984b7d
Quelldatensatz
uspto-grants-2015_10
Patentnummer
US09169270B2

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