Reaction equation
[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]Participants
Procedure
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.
Workup
- stirringAfter stirring for 20 h at RT
- customthe reaction mixture was quenched by addition of sat. NaHCO3 (100 mL), EtOAc (150 mL)
- additionwas added
- customthe phases were separated
- extractionThe aqueous phase was extracted with EtOAc (2×75 mL)
- dry with materialthe combined organic extracts were dried over MgSO4
- concentrationconcentrated in vacuo
- customPurification by column chromatography (10-50% EtOAc in hexanes)
Sources & evidence
- ORD record
- ord-c43bdbacf2ad467f9905eb48093d2d0a
- Source dataset
- uspto-grants-2012_06
- Patent number
- US08202861B2
Linked notes
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