Synthesis of β-hydroxyacetamides from unactivated ethyl acetates under base-free conditions and microwave irradiation

The amidation of unactivated ethyl esters with achiral and chiral 1,2-amino alcohols under microwave irradiation and base-free conditions is described. This procedure provides a convenient method for the synthesis of β-hydroxyacetamides bearing pyrazole, imidazole, and benzimidazole groups in high yields and without racemization. The protocol described herein is environmentally friendly and allows for the preparation of a wide variety of β-hydroxyacetamides, which are key intermediates in the synthesis of oxazolines and other derivatives of biological interest.

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(S)-N-(2-Hydroxy-1-phenylethyl)-2-(pyrrolidin-1-yl)acetamideC14H20N2O2Ee >98%[α]D28 = +30.66 (c 3.0, CHCl3)Source of chirality: Asymmetric synthesisAbsolute configuration: (S)

(S)-N-(2-Hydroxy-1-phenylethyl)-2-(piperidin-1-yl)acetamideC15H22N2O2Ee >98%[α]D28 = +28.0 (c 3.0, CHCl3)Source of chirality: Asymmetric synthesisAbsolute configuration: (S)

(S)-N-(2-Hydroxy-1-phenylethyl)-2-morpholinacetamideC14H20N2O3Ee >98%[α]D28 = +36.0 (c 3.0, CHCl3)Source of chirality: Asymmetric synthesisAbsolute configuration: (S)

(S)-N-(2-Hydroxy-1-phenylethyl)-2-(1H-benzo[d]imidazol-1-yl)acetamideC17H17N3O2Ee >98%[α]D28 = +86.8 (c 3.0, DMSO)Source of chirality: Asymmetric synthesisAbsolute configuration: (S)

(S)-N-(2-Hydroxy-1-phenylethyl)-2-(2H-benzo[d][1,2,3]triazol-2-yl)acetamideC16H16N4O2Ee >98%[α]D28 = +128.0 (c 3.0, DMSO)Source of chirality: Asymmetric synthesisAbsolute configuration: (S)

(S)-N-(2-Hydroxy-1-phenylethyl)-2-(1H-benzo[d][1,2,3]triazol-1-yl)acetamideC16H16N4O2Ee >98%[α]D28 = +130.65 (c 3.0, DMSO)Source of chirality: Asymmetric synthesisAbsolute configuration: (S)

(S)-N-(1-Hydroxy-3-phenylpropan-2-yl)-2-(1H-pyrazol-1-yl)acetamideC14H17N3O2Ee >98%[α]D28 = −24.0 (c 1.0, MeOH)Source of chirality: Asymmetric synthesisAbsolute configuration: (S)

(S)-N-(1-Hydroxy-3-phenylpropan-2-yl)-2-(1H-imidazol-1-yl)acetamideC14H17N3O2Ee >98%[α]D28 = −10.0 (c 1.0, MeOH)Source of chirality: Asymmetric synthesisAbsolute configuration: (S)

(S)-N-(1-Hydroxy-3-phenylpropan-2-yl)-2-(1H-benzo[d]imidazol-1-yl)acetamideC18H19N3O2Ee >98%[α]D28 = −12.0 (c 1.0, MeOH)Source of chirality: Asymmetric synthesisAbsolute configuration: (S)

(R)-N-(2-Hydroxy-1-phenylethyl)-2-(1H-pyrazol-1-yl)acetamideC13H15N3O2Ee >98%[α]D28 = −96.0 (c 1.0, MeOH)Source of chirality: Asymmetric synthesisAbsolute configuration: (R)

(R)-N-(2-Hydroxy-1-phenylethyl)-2-(1H-imidazol-1-yl)acetamideC13H15N3O2Ee >98%[α]D28 = −105.2 (c 1.0, MeOH)Source of chirality: Asymmetric synthesisAbsolute configuration: (R)

(R)-N-(2-Hydroxy-1-phenylethyl)-2-(1H-benzo[d]imidazol-1-yl)acetamideC17H17N3O2Ee >98%[α]D28 = −108.0 (c 1.0, MeOH)Source of chirality: Asymmetric synthesisAbsolute configuration: (R)

(S)-N-(1-Hydroxypropan-2-yl)-2-(1H-pyrazol-1-yl)acetamideC8H13N3O2Ee >98%[α]D28 = −15.3 (c 1.0, MeOH)Source of chirality: Asymmetric synthesisAbsolute configuration: (S)

(S)-N-(1-Hydroxypropan-2-yl)-2-(1H-imidazol-1-yl)acetamideC8H13N3O2Ee >98%[α]D28 = −8.0 (c 1.0, MeOH)Source of chirality: Asymmetric synthesisAbsolute configuration: (S)

(S)-N-(1-Hydroxypropan-2-yl)-2-(1H-benzo[d]imidazol-1-yl)acetamideC12H15N3O2Ee >98%[α]D28 = −12.0 (c 1.0, MeOH)Source of chirality: Asymmetric synthesisAbsolute configuration: (S)

(S)-N-(1-Hydroxy-3-methylbutan-2-yl)-2-(1H-pyrazol-1-yl)acetamideC10H17N3O2Ee >98%[α]D28 = −32.0 (c 1.0, MeOH)Source of chirality: Asymmetric synthesisAbsolute configuration: (S)

(S)-N-(1-Hydroxy-3-methylbutan-2-yl)-2-(1H-imidazol-1-yl)acetamideC10H17N3O2Ee >98%[α]D28 = −13.8 (c 0.5, MeOH)Source of chirality: Asymmetric synthesisAbsolute configuration: (S)

(S)-N-(1-Hydroxy-3-methylbutan-2-yl)-2-(1H-benzo[d]imidazol-1-yl)acetamideC14H19N3O2Ee >98%[α]D28 = −8.0 (c 1.0, MeOH)Source of chirality: Asymmetric synthesisAbsolute configuration: (S)