1.1: sodium hydride / dimethyl sulfoxide / 0.5 h / 25 °C 1.2: 16 h / 0 - 25 °C 2.1: hydrazine / water; methanol / 16 h / 25 - 70 °C 3.1: sodium nitrite; acetic acid / 0.5 h / 25 °C 4.1: toluene / 1 h / 110 °C 4.2: 2 h / 100 °C 4.3: 25 °C / pH 10 5.1: methanol / 2.5 h / 18 - 45 °C View Scheme

1.1: N-ethyl-N,N-diisopropylamine / dichloromethane / 0.5 h / 20 - 25 °C 1.2: 3 h / 20 - 25 °C 2.1: lithium hexamethyldisilazane / tetrahydrofuran / 1 h / -25 - -15 °C 2.2: 1.5 h / -25 - -15 °C 2.3: 0.08 h 3.1: N-ethyl-N,N-diisopropylamine / tetrahydrofuran / 2 h / 20 - 25 °C 4.1: sodium hydrogencarbonate; sodium dithionite / water; acetone / 2 h / 20 - 25 °C 5.1: sodium azide; acetic acid / toluene; water / 1 h / 5 - 10 °C 6.1: hydrogenchloride; water / toluene; methanol / 2 h / 25 - 30 °C 6.2: pH > 8 View Scheme

<b>Multi-step reaction with 4 steps<br /> </b>1.1: sodium iodide; 1,3,5-trishydroxybenzene; sodium nitrite / N,N-dimethyl-formamide / 5 - 30 &deg;C / Inert atmosphere<br />2.1: (S)-3,3-diphenyl-1-methyltetrahydro-1H,3H-pyrrolo[1,2-c][1,3,2]oxazaborol; BH₃*N,N-diethylanilline / toluene / 25 - 40 &deg;C / Inert atmosphere<br />3.1: triphenylphosphine / toluene / 2 h / 0 - 10 &deg;C<br />4.1: hydrogenchloride; zinc / water; methanol / -5 - 0 &deg;C<br />4.2: 0.25 h / 30 &deg;C<br />4.3: 20 - 25 &deg;C<br /> <br /> &nbsp;

<b>Multi-step reaction with 3 steps<br /> </b>1.1: (S)-3,3-diphenyl-1-methyltetrahydro-1H,3H-pyrrolo[1,2-c][1,3,2]oxazaborol; BH₃*N,N-diethylanilline / toluene / 25 - 40 &deg;C / Inert atmosphere<br />2.1: triphenylphosphine / toluene / 2 h / 0 - 10 &deg;C<br />3.1: hydrogenchloride; zinc / water; methanol / -5 - 0 &deg;C<br />3.2: 0.25 h / 30 &deg;C<br />3.3: 20 - 25 &deg;C<br /> <br /> &nbsp;

<b>Multi-step reaction with 3 steps<br /> </b>1.1: triphenylphosphine; di-isopropyl azodicarboxylate / toluene / 5 - 10 &deg;C<br />2.1: hydrogenchloride; zinc / methanol / -5 - 0 &deg;C<br />2.2: 0.25 h / 10 - 30 &deg;C<br />3.1: methanol / 12 h / 20 - 25 &deg;C<br /> <br /> &nbsp;

Stage #1: <a href="#" onclick="return RXDsubstances(event, this, '21913989', constants.ctx, '0')">trans-(1R,2S)-2-(3,4-difluorophenyl)-1-nitrocyclopropane</a> <b>With</b>&nbsp; <a href="#" onclick="return RXDsubstances(event, this, '1098214', constants.ctx, '0')">hydrogenchloride</a>;&nbsp;<a href="#" onclick="return RXDsubstances(event, this, '8973685', constants.ctx, '0')">zinc</a>&nbsp;<b>in</b>&nbsp; <a href="#" onclick="return RXDsubstances(event, this, '1098229', constants.ctx, '0')">methanol</a>;&nbsp;<a href="#" onclick="return RXDsubstances(event, this, '3587155', constants.ctx, '0')">water</a> <br />T=-5 - 0&deg;C;&nbsp;<br />Stage #2: <b>With</b>&nbsp; <a href="#" onclick="return RXDsubstances(event, this, '3587154', constants.ctx, '0')">ammonia</a>&nbsp;<b>in</b>&nbsp; <a href="#" onclick="return RXDsubstances(event, this, '1730800', constants.ctx, '0')">dichloromethane</a>;&nbsp;<a href="#" onclick="return RXDsubstances(event, this, '3587155', constants.ctx, '0')">water</a> <br />T=30&deg;C;&nbsp;0.25&nbsp;h;&nbsp;<br />Stage #3: <a href="#" onclick="return RXDsubstances(event, this, '2691094', constants.ctx, '0')">(R)-(-)-α-hydroxybenzeneacetic acid</a> &nbsp;<b>in</b>&nbsp; <a href="#" onclick="return RXDsubstances(event, this, '1098229', constants.ctx, '0')">methanol</a> <br />T=20 - 25&deg;C;&nbsp;<br /> <br /> &nbsp;

<b>Multi-step reaction with 5 steps<br /> </b>1.1: AlCl₃, aluminium chloride / dichloromethane / 4 h / 20 - 25 &deg;C / Industry scale<br />2.1: sodium iodide; 1,3,5-trishydroxybenzene; sodium nitrite / N,N-dimethyl-formamide / 5 - 30 &deg;C / Inert atmosphere<br />3.1: (S)-3,3-diphenyl-1-methyltetrahydro-1H,3H-pyrrolo[1,2-c][1,3,2]oxazaborol; BH₃*N,N-diethylanilline / toluene / 25 - 40 &deg;C / Inert atmosphere<br />4.1: triphenylphosphine / toluene / 2 h / 0 - 10 &deg;C<br />5.1: hydrogenchloride; zinc / water; methanol / -5 - 0 &deg;C<br />5.2: 0.25 h / 30 &deg;C<br />5.3: 20 - 25 &deg;C<br /> <br /> &nbsp;

<b>Multi-step reaction with 6 steps<br /> </b>1.1: sulfuric acid / 72 h / 60 &deg;C<br />2.1: sodium hydride / dimethyl sulfoxide / 0.5 h / 25 &deg;C<br />2.2: 16 h / 0 - 25 &deg;C<br />3.1: hydrazine / water; methanol / 16 h / 25 - 70 &deg;C<br />4.1: sodium nitrite; acetic acid / 0.5 h / 25 &deg;C<br />5.1: toluene / 1 h / 110 &deg;C<br />5.2: 2 h / 100 &deg;C<br />5.3: 25 &deg;C / pH 10<br />6.1: methanol / 2.5 h / 18 - 45 &deg;C<br /> <br /> &nbsp;

<b>Multi-step reaction with 6 steps<br /> </b>1.1: pyridine / acetone / 0 h / 0 - 30 &deg;C<br />1.2: 0 - 5 &deg;C<br />2.1: sodium hydride / dimethyl sulfoxide / 1 h / 25 - 30 &deg;C<br />2.2: 3 h / 25 - 30 &deg;C<br />3.1: hydrazine hydrate / methanol / 12 h / 60 - 65 &deg;C<br />4.1: sodium nitrite; acetic acid / 0.5 h / 25 &deg;C<br />5.1: toluene / 1 h / 110 &deg;C<br />5.2: 2 h / 100 &deg;C<br />5.3: 25 &deg;C / pH 10<br />6.1: methanol / 2.5 h / 18 - 45 &deg;C<br /> <br /> &nbsp;