Sequential enzymatic procedure for the preparation of enantiomerically pure 2-heteroaryl-2-hydroxyacetic acids

Starting from the racemic 2-benzofuranyl- and 2-benzo[b]thiophenyl-2-hydroxyacetic acid ethyl esters as substrates, a general method was developed for the efficient synthesis of the corresponding highly enantiomerically enriched (ee up to 99%) (R)- and (S)-2-heteroaryl-2-hydroxyacetic acids.

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(S)-2-(Benzofuran-2-yl)-2-hydroxyacetic acidC10H8O4[α]D20=-27 (c 1.0, CH3OH)ee >99% on tandem Chiralpak IC-IA HPLC columnsSource of chirality: enzymatic resolutionAbsolute configuration: (S)

(R)-2-(Benzo[b]thiophen-2-yl)-2-hydroxyacetic acidC10H8SO3[α]D20=-48.3 (c 1.0, CH3OH)ee >99% on Chiralpak IC HPLC columnSource of chirality: enzymatic resolutionAbsolute configuration: (R)

(R)-2-(Benzofuran-3-yl)-2-hydroxyacetic acidC10H8O4[α]D20=+3 (c 1.0, CH3OH)ee >99% on tandem Chiralkpak IC-IB HPLC columnsSource of chirality: enzymatic resolutionAbsolute configuration: (R)

(S)-2-(Benzo[b]thiophen-3-yl)-2-hydroxyacetic acidC10H8SO3[α]D20=-48.3 (c 1.0, CH3OH)ee >99% on Chiralpak IC HPLC columnSource of chirality: enzymatic resolutionAbsolute configuration: (S)