Imidazole → (R)-Toluene-4-sulfonic acid 2-(tert-butyl-dimethyl-silanyloxy)-2-(6-chloro-pyridin-3-yl)-ethyl ester

HRID 495715Notes

Reaction equation

HRID 495715 reaction equation
[Cl:1][C:2]1[N:7]=[CH:6][C:5]([C@@H:8]([OH:21])[CH2:9][O:10][S:11]([C:14]2[CH:19]=[CH:18][C:17]([CH3:20])=[CH:16][CH:15]=2)(=[O:13])=[O:12])=[CH:4][CH:3]=1.N1C=CN=C1.[Si:27](Cl)([C:30]([CH3:33])([CH3:32])[CH3:31])([CH3:29])[CH3:28].C(OCC)(=O)C>CN(C)C=O>[C:30]([Si:27]([CH3:29])([CH3:28])[O:21][C@H:8]([C:5]1[CH:6]=[N:7][C:2]([Cl:1])=[CH:3][CH:4]=1)[CH2:9][O:10][S:11]([C:14]1[CH:15]=[CH:16][C:17]([CH3:20])=[CH:18][CH:19]=1)(=[O:13])=[O:12])([CH3:33])([CH3:32])[CH3:31]

Participants

6

Reactant 4

HCID 795ImidazoleHCID 8857Ethyl AcetateHCID 28928tert-Butyldimethylsilyl chlorideHCID 11738935(R)-Toluene-4-sulfonic acid 2-(6-chloro-pyridin-3-yl)-2-hydroxy-ethyl ester

Product 1

HCID 12972452(R)-Toluene-4-sulfonic acid 2-(tert-butyl-dimethyl-silanyloxy)-2-(6-chloro-pyridin-3-yl)-ethyl esterYield 84.7%

Reagents, catalysts & solvents 1

HCID 6228DimethylformamideSolvent

Conditions

Temperature
50 °C

Procedure

To a cooled (50° C.), stirred solution of (R)-toluene-4-sulfonic acid 2-(6-chloro-pyridin-3-yl)-2-hydroxy-ethyl ester (4.9 g) and imidazole (2.0 g) in anhydrous dimethyformamide (14 mL) was added t-butyldimethylsilyl chloride (2.8 g). The reaction mixture was allowed to warm to room temperature and stirring was continued for 18 h. Ethyl acetate was added, followed by washing with water (2×), drying over sodium sulfate and concentration in vacuo to afford an oil. Chromatography (Flash 40M®) utilizing 10% ethyl acetate/hexanes afforded 5.6 g of the title compound (I-2e) as a colorless oil.

Workup

  1. temperatureto warm to room temperature
  2. washby washing with water (2×)
  3. dry with materialdrying over sodium sulfate and concentration in vacuo
  4. customto afford an oil

Sources & evidence

ORD record
ord-46e54779df7f45b28353f87dace4c1ad
Source dataset
uspto-grants-2005_09
Patent number
US06939867B2

Reaction notes

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