A Practical Procedure for Reduction of Primary, Secondary and Tertiary Amides to Amines
References
mary and secondary amides, the product amine usual-
ly may be directly precipitated after the reaction by
adding HCl to the reaction mixture, thus allowing
a simple isolation. This reagent system provides a con-
venient and general option for the reduction of a pri-
mary, secondary or tertiary amide, in contrast to
many other reagent systems which are specific for
a certain type of amide.
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Experimental Section
General Procedure for 28 or 38 Amide Reduction
To a dry 1-neck, 25-mL, round-bottom flask equipped with
a football shaped magnetic stir bar was charged amide
(3.00 mmol, 1 equiv.) and Ru3(CO)12 (19.2 mg, 0.03 mmol,
1 mol%). The flask was sealed with a rubber septum and
a nitrogen inlet needle was inserted in the septum. The flask
was evacuated and filled with nitrogen. Toluene (1.5 mL)
was charged followed by 1,1,3,3-tetramethyldisiloxane
(TMDS, 2.12 mL, 12.00 mmol, 4 equiv.). The reaction mix-
ture was stirred at room temperature for 10 min and then
placed in a 508C oil bath and stirred for 24 h, or until com-
plete conversion by HPLC analysis. The reaction mixture
was cooled to room temperature.
HCl salt formation (works for most secondary amines):
The reaction mixture was treated with 4M HCl in dioxane
(3.0 mL) and EtOAc (2–10 mL), stirred at room tempera-
ture for 30 min, and the resultant solid was filtered, washed
with EtOAc and dried under vacuum. If necessary, the salt
was recrystallized to upgrade the purity.
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Free base isolation (used for tertiary amines or if the free
base of a secondary amine is desired): The reaction mixture
was treated with aqueous 1N NaOH and CH2Cl2 and stirred
at room temperature for 30 min. The layers were separated,
and the organic phase was dried (Na2SO4), filtered and con-
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General Procedure for Primary Amide Reduction
To a dry 1-neck, 25-mL, round-bottom flask equipped with
a football shaped magnetic stir bar was charged amide
(3.00 mmol, 1 equiv.) and Ru3(CO)12 (19.2 mg, 0.03 mmol,
1 mol%). The flask was sealed with a rubber septum and
a nitrogen inlet needle was inserted in the septum. The flask
was evacuated and filled with nitrogen. Toluene (1.5 mL)
was charged followed by 1,1,3,3-tetramethyldisiloxane
(TMDS, 3.18 mL, 18.00 mmol, 6 equiv.). The reaction mix-
ture was stirred at room temperature for 10 min and then
placed in a 708C oil bath and stirred for 24 h, or until com-
plete conversion by HPLC analysis. The reaction mixture
was cooled to room temperature. HCl salt formation was
done as described above for reductions of secondary amides.
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1
Procedures, spectral data, and copies of H and 13C NMR
spectra are available in the Supporting Information.
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Adv. Synth. Catal. 2013, 355, 47 – 52
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