Pyridine → Thiazole-2-carboxylic acid 4-tert-butoxycarbonylamino-phenyl ester

HRID 219557

Reaktionsgleichung

Reaktionsgleichung von HRID 219557
[Si]([C:5]1[S:6][CH:7]=[CH:8][N:9]=1)(C)(C)C.[C:10](Cl)(Cl)=[O:11].C1(C)C=CC=CC=1.[C:21]([NH:28][C:29]1[CH:34]=[CH:33][C:32]([OH:35])=[CH:31][CH:30]=1)([O:23][C:24]([CH3:27])([CH3:26])[CH3:25])=[O:22].N1C=CC=CC=1>C(Cl)Cl>[C:24]([O:23][C:21]([NH:28][C:29]1[CH:30]=[CH:31][C:32]([O:35][C:10]([C:5]2[S:6][CH:7]=[CH:8][N:9]=2)=[O:11])=[CH:33][CH:34]=1)=[O:22])([CH3:27])([CH3:25])[CH3:26]

Komponenten

7

Edukt 5

HCID 1049PyridineHCID 1140TolueneHCID 6371PhosgeneHCID 5884532-TrimethylsilylthiazoleHCID 2756771N-Boc-4-hydroxyaniline

Produkt 1

HCID 57936391Thiazole-2-carboxylic acid 4-tert-butoxycarbonylamino-phenyl esterAusbeute 12 %

Reagenzien, Katalysatoren, Lösungsmittel 1

HCID 6344DichloromethaneLösungsmittel2×

Versuchsvorschrift

To a solution of 2-TMS-thiazole (2.25 mL, 14.1 mmol) in DCM (5 mL) at 0° C. was slowly added a solution of phosgene in toluene (20%, 7.45 mL, 14.1 mmol) over 15 Min. After stirring for 2 h at RT, the resulting solution was slowly added via syringe to a solution of N—BOC-4-hydroxyaniline (4.39 g, 21.2 mmol) and pyridine (2.3 mL, 28.2 mmol) in DCM (100 mL) at 0° C. After stirring for 20 h at RT, the reaction mixture was quenched by addition of sat. NaHCO3 (100 mL), EtOAc (150 mL) was added, and the phases were separated. The aqueous phase was extracted with EtOAc (2×75 mL), and the combined organic extracts were dried over MgSO4 and concentrated in vacuo. Purification by column chromatography (10-50% EtOAc in hexanes) afforded the product as a green solid (518 mg, 12%). 1H-NMR (400 MHz, DMSO-d6) δ 9.49 (s, 1H), 8.29 (d, J=3.0 Hz, 1H), 8.22 (d, J=3.0 Hz, 1H), 7.53 (d, J=8.9 Hz, 2H), 7.23 (d, J=6.9 Hz, 2H), 1.48 (s, 9H). LC/MS (10-99%) M/Z: M+1 obs=321.1; tR=2.94 min.

Aufarbeitung

  1. stirringAfter stirring for 20 h at RT
  2. customthe reaction mixture was quenched by addition of sat. NaHCO3 (100 mL), EtOAc (150 mL)
  3. additionwas added
  4. customthe phases were separated
  5. extractionThe aqueous phase was extracted with EtOAc (2×75 mL)
  6. dry with materialthe combined organic extracts were dried over MgSO4
  7. concentrationconcentrated in vacuo
  8. customPurification by column chromatography (10-50% EtOAc in hexanes)

Quellen und Nachweise

ORD-Eintrag
ord-c43bdbacf2ad467f9905eb48093d2d0a
Quelldatensatz
uspto-grants-2012_06
Patentnummer
US08202861B2

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