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

HRID 1875322Notes

Reaction equation

HRID 1875322 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

7

Reactant 5

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

Product 1

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

Reagents, catalysts & solvents 1

HCID 6344DichloromethaneSolvent2×

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

  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)

Sources & evidence

ORD record
ord-2b2a82e9bdff40e28cd6a6827885bc7a
Source dataset
uspto-grants-2012_11
Patent number
US08309543B2

Reaction notes

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