Sodium Carbonate → HCID 90022085, Verbindung

HRID 1754835Notizen

Reaktionsgleichung

Reaktionsgleichung von HRID 1754835
[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.[C:35]1(B(O)O)[CH:40]=[CH:39][CH:38]=[CH:37][CH:36]=1.C(=O)([O-])[O-].[Na+].[Na+]>C1(C)C=CC=CC=1.CO.O.[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]([C:35]3[CH:40]=[CH:39][CH:38]=[CH:37][CH:36]=3)[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

6

Edukt 3

HCID 10340Sodium CarbonateHCID 66827Phenylboronic AcidHCID 90022152(+/-)-2-bromo-4-(5-chloro-2-ethoxycarbonylmethoxy-phenyl)-6,7-dihydro-4H-thiazolo[5,4-c]pyridine-5-carboxylic acid benzyl ester

Produkt 1

HCID 90022085HCID 90022085, Verbindung

Reagenzien, Katalysatoren, Lösungsmittel 2

HCID 11979704Tetrakis(triphenylphosphine)palladiumKatalysatorHCID 70394911MeOH toluene waterLösungsmittel

Reaktionsbedingungen

Temperatur
100 °C

Versuchsvorschrift

To a mixture 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 (63 mg, 0.12 mmol, 1.00 eq.), phenylboronic acid (15 mg, 0.12 mmol, 1.00 eq.) and sodium carbonate (50 mg, 0.47 mmol, 4.00 eq.) in toluene/MeOH/Water 20:4:1 (4 mL), tetrakis(triphenylphosphine) palladium (0) (6.8 mg, 6 μmol, 0.05 eq.) was added and the mixture was stirred at 100° C. for 18 hours. The mixture was allowed to cool to r.t. and concentrated in vacuo. The residue was partitioned between AcOEt (25 mL) and water (25 mL). The layers were separated. The org. phase was washed with sat. aq. NaCl soln. (1×12 mL), dried over MgSO4 and filtered through Celite. The filtrate was concentrated in vacuo. The residue 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. customThe residue was partitioned between AcOEt (25 mL) and water (25 mL)
  4. customThe layers were separated
  5. washphase was washed with sat. aq. NaCl soln
  6. dry with material(1×12 mL), dried over MgSO4
  7. filtrationfiltered through Celite
  8. concentrationThe filtrate was concentrated in vacuo
  9. dissolutionThe residue was dissolved in DMF (0.5 mL)
  10. addition(0.5 mL) was added
  11. stirringThe resulting solution was stirred at r.t. for 18 hours
  12. filtrationfiltered
  13. custompurified by prep
  14. concentrationHPLC (column: Atlantis, 30×75 mm, 10 um, UV/MS, acidic conditions) and concentrated in vacuo

Quellen und Nachweise

ORD-Eintrag
ord-8fd186de5ef449a689fb86344d739e34
Quelldatensatz
uspto-grants-2015_10
Patentnummer
US09169270B2

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