magnesium bromide in diethyl ether; benzene T=0 - 20°C; SEM deprotection; 11 h;

1: 47 percent / LDA; Py*HCl / tetrahydrofuran / -78 - 20 °C 2: 81 percent / MgBr2*Et2O; EtSH / diethyl ether; benzene / 11 h / 0 - 20 °C View Scheme

Stage #1: <b>With</b>&nbsp; <a href="#" onclick="return RXDsubstances(event, this, '3570522', constants.ctx, '0')">tetrabutyl ammonium fluoride</a>&nbsp;<b>in</b>&nbsp; <a href="#" onclick="return RXDsubstances(event, this, '102391', constants.ctx, '0')">tetrahydrofuran</a> <br />T=40 - 50&deg;C;&nbsp;desilylation;&nbsp;5&nbsp;h;&nbsp;<br />Stage #2: &nbsp;<b>in</b>&nbsp; <a href="#" onclick="return RXDsubstances(event, this, '1731042', constants.ctx, '0')">chloroform</a>;&nbsp;<a href="#" onclick="return RXDsubstances(event, this, '969212', constants.ctx, '0')">benzene</a> <br />lactonization;&nbsp;&nbsp;Heating;&nbsp;&nbsp;Further stages.;&nbsp;<br /> &nbsp;

<b>Multi-step reaction with 16 steps<br /> </b>1.1: 83 percent / NaBH₄ / ethanol / 20 &deg;C<br />2.1: 90 percent / acetic acid / 2 h / 80 &deg;C<br />3.1: 99 percent / H₂ / 10percent Pd/C / ethyl acetate / 6 h / 2482.38 Torr<br />4.1: 82 percent / LiAlH₄ / diethyl ether / 24 h / Heating<br />5.1: 100 percent / DMAP / pyridine / 16 h / 20 &deg;C<br />6.1: 66 percent / PPL / dimethylsulfoxide; aq. phosphate buffer / 2.5 h / 20 &deg;C / pH 7.8<br />7.1: 100 percent / imidazole / dimethylformamide / 7 h / 20 &deg;C<br />8.1: 100 percent / K₂CO₃ / methanol / 1.5 h / 20 &deg;C<br />9.1: 100 percent / oxalyl chloride; DMSO; Et₃N / CH₂Cl₂ / -78 - -40 &deg;C<br />10.1: 90 percent / NaOMe / methanol / 20 &deg;C<br />11.1: 93 percent / i-Pr₂NEt / CH₂Cl₂ / 0 - 20 &deg;C<br />12.1: 95 percent / 2-methyl-2-butene; NaClO₂; NaH₂PO₄ / 2-methyl-propan-2-ol; H₂O / 20 &deg;C<br />13.1: CDI / tetrahydrofuran / 3 h / 20 &deg;C<br />13.2: 20 percent / KHMDS / tetrahydrofuran; toluene / 7 h / 0 - 20 &deg;C<br />14.1: CDI / tetrahydrofuran / 3 h / 20 &deg;C<br />14.2: 64 percent / n-BuLi / tetrahydrofuran; hexane / 4.5 h / -78 &deg;C<br />15.1: 85 percent / CuCN / tetrahydrofuran / 3.5 h / 10 &deg;C<br />16.1: TBAF / tetrahydrofuran / 5 h / 40 - 50 &deg;C<br />16.2: 62 percent / benzene; CHCl₃ / Heating<br /> <br /> &nbsp;

<b>Multi-step reaction with 15 steps<br /> </b>1.1: 90 percent / acetic acid / 2 h / 80 &deg;C<br />2.1: 99 percent / H₂ / 10percent Pd/C / ethyl acetate / 6 h / 2482.38 Torr<br />3.1: 82 percent / LiAlH₄ / diethyl ether / 24 h / Heating<br />4.1: 100 percent / DMAP / pyridine / 16 h / 20 &deg;C<br />5.1: 66 percent / PPL / dimethylsulfoxide; aq. phosphate buffer / 2.5 h / 20 &deg;C / pH 7.8<br />6.1: 100 percent / imidazole / dimethylformamide / 7 h / 20 &deg;C<br />7.1: 100 percent / K₂CO₃ / methanol / 1.5 h / 20 &deg;C<br />8.1: 100 percent / oxalyl chloride; DMSO; Et₃N / CH₂Cl₂ / -78 - -40 &deg;C<br />9.1: 90 percent / NaOMe / methanol / 20 &deg;C<br />10.1: 93 percent / i-Pr₂NEt / CH₂Cl₂ / 0 - 20 &deg;C<br />11.1: 95 percent / 2-methyl-2-butene; NaClO₂; NaH₂PO₄ / 2-methyl-propan-2-ol; H₂O / 20 &deg;C<br />12.1: CDI / tetrahydrofuran / 3 h / 20 &deg;C<br />12.2: 20 percent / KHMDS / tetrahydrofuran; toluene / 7 h / 0 - 20 &deg;C<br />13.1: CDI / tetrahydrofuran / 3 h / 20 &deg;C<br />13.2: 64 percent / n-BuLi / tetrahydrofuran; hexane / 4.5 h / -78 &deg;C<br />14.1: 85 percent / CuCN / tetrahydrofuran / 3.5 h / 10 &deg;C<br />15.1: TBAF / tetrahydrofuran / 5 h / 40 - 50 &deg;C<br />15.2: 62 percent / benzene; CHCl₃ / Heating<br /> <br /> &nbsp;

<b>Multi-step reaction with 14 steps<br /> </b>1.1: 99 percent / H₂ / 10percent Pd/C / ethyl acetate / 6 h / 2482.38 Torr<br />2.1: 82 percent / LiAlH₄ / diethyl ether / 24 h / Heating<br />3.1: 100 percent / DMAP / pyridine / 16 h / 20 &deg;C<br />4.1: 66 percent / PPL / dimethylsulfoxide; aq. phosphate buffer / 2.5 h / 20 &deg;C / pH 7.8<br />5.1: 100 percent / imidazole / dimethylformamide / 7 h / 20 &deg;C<br />6.1: 100 percent / K₂CO₃ / methanol / 1.5 h / 20 &deg;C<br />7.1: 100 percent / oxalyl chloride; DMSO; Et₃N / CH₂Cl₂ / -78 - -40 &deg;C<br />8.1: 90 percent / NaOMe / methanol / 20 &deg;C<br />9.1: 93 percent / i-Pr₂NEt / CH₂Cl₂ / 0 - 20 &deg;C<br />10.1: 95 percent / 2-methyl-2-butene; NaClO₂; NaH₂PO₄ / 2-methyl-propan-2-ol; H₂O / 20 &deg;C<br />11.1: CDI / tetrahydrofuran / 3 h / 20 &deg;C<br />11.2: 20 percent / KHMDS / tetrahydrofuran; toluene / 7 h / 0 - 20 &deg;C<br />12.1: CDI / tetrahydrofuran / 3 h / 20 &deg;C<br />12.2: 64 percent / n-BuLi / tetrahydrofuran; hexane / 4.5 h / -78 &deg;C<br />13.1: 85 percent / CuCN / tetrahydrofuran / 3.5 h / 10 &deg;C<br />14.1: TBAF / tetrahydrofuran / 5 h / 40 - 50 &deg;C<br />14.2: 62 percent / benzene; CHCl₃ / Heating<br /> <br /> &nbsp;

<b>Multi-step reaction with 12 steps<br /> </b>1.1: 100 percent / DMAP / pyridine / 16 h / 20 &deg;C<br />2.1: 66 percent / PPL / dimethylsulfoxide; aq. phosphate buffer / 2.5 h / 20 &deg;C / pH 7.8<br />3.1: 100 percent / imidazole / dimethylformamide / 7 h / 20 &deg;C<br />4.1: 100 percent / K₂CO₃ / methanol / 1.5 h / 20 &deg;C<br />5.1: 100 percent / oxalyl chloride; DMSO; Et₃N / CH₂Cl₂ / -78 - -40 &deg;C<br />6.1: 90 percent / NaOMe / methanol / 20 &deg;C<br />7.1: 93 percent / i-Pr₂NEt / CH₂Cl₂ / 0 - 20 &deg;C<br />8.1: 95 percent / 2-methyl-2-butene; NaClO₂; NaH₂PO₄ / 2-methyl-propan-2-ol; H₂O / 20 &deg;C<br />9.1: CDI / tetrahydrofuran / 3 h / 20 &deg;C<br />9.2: 20 percent / KHMDS / tetrahydrofuran; toluene / 7 h / 0 - 20 &deg;C<br />10.1: CDI / tetrahydrofuran / 3 h / 20 &deg;C<br />10.2: 64 percent / n-BuLi / tetrahydrofuran; hexane / 4.5 h / -78 &deg;C<br />11.1: 85 percent / CuCN / tetrahydrofuran / 3.5 h / 10 &deg;C<br />12.1: TBAF / tetrahydrofuran / 5 h / 40 - 50 &deg;C<br />12.2: 62 percent / benzene; CHCl₃ / Heating<br /> <br /> &nbsp;

<b>Multi-step reaction with 13 steps<br /> </b>1.1: 82 percent / LiAlH₄ / diethyl ether / 24 h / Heating<br />2.1: 100 percent / DMAP / pyridine / 16 h / 20 &deg;C<br />3.1: 66 percent / PPL / dimethylsulfoxide; aq. phosphate buffer / 2.5 h / 20 &deg;C / pH 7.8<br />4.1: 100 percent / imidazole / dimethylformamide / 7 h / 20 &deg;C<br />5.1: 100 percent / K₂CO₃ / methanol / 1.5 h / 20 &deg;C<br />6.1: 100 percent / oxalyl chloride; DMSO; Et₃N / CH₂Cl₂ / -78 - -40 &deg;C<br />7.1: 90 percent / NaOMe / methanol / 20 &deg;C<br />8.1: 93 percent / i-Pr₂NEt / CH₂Cl₂ / 0 - 20 &deg;C<br />9.1: 95 percent / 2-methyl-2-butene; NaClO₂; NaH₂PO₄ / 2-methyl-propan-2-ol; H₂O / 20 &deg;C<br />10.1: CDI / tetrahydrofuran / 3 h / 20 &deg;C<br />10.2: 20 percent / KHMDS / tetrahydrofuran; toluene / 7 h / 0 - 20 &deg;C<br />11.1: CDI / tetrahydrofuran / 3 h / 20 &deg;C<br />11.2: 64 percent / n-BuLi / tetrahydrofuran; hexane / 4.5 h / -78 &deg;C<br />12.1: 85 percent / CuCN / tetrahydrofuran / 3.5 h / 10 &deg;C<br />13.1: TBAF / tetrahydrofuran / 5 h / 40 - 50 &deg;C<br />13.2: 62 percent / benzene; CHCl₃ / Heating<br /> <br /> &nbsp;

<b>Multi-step reaction with 11 steps<br /> </b>1.1: 66 percent / PPL / dimethylsulfoxide; aq. phosphate buffer / 2.5 h / 20 &deg;C / pH 7.8<br />2.1: 100 percent / imidazole / dimethylformamide / 7 h / 20 &deg;C<br />3.1: 100 percent / K₂CO₃ / methanol / 1.5 h / 20 &deg;C<br />4.1: 100 percent / oxalyl chloride; DMSO; Et₃N / CH₂Cl₂ / -78 - -40 &deg;C<br />5.1: 90 percent / NaOMe / methanol / 20 &deg;C<br />6.1: 93 percent / i-Pr₂NEt / CH₂Cl₂ / 0 - 20 &deg;C<br />7.1: 95 percent / 2-methyl-2-butene; NaClO₂; NaH₂PO₄ / 2-methyl-propan-2-ol; H₂O / 20 &deg;C<br />8.1: CDI / tetrahydrofuran / 3 h / 20 &deg;C<br />8.2: 20 percent / KHMDS / tetrahydrofuran; toluene / 7 h / 0 - 20 &deg;C<br />9.1: CDI / tetrahydrofuran / 3 h / 20 &deg;C<br />9.2: 64 percent / n-BuLi / tetrahydrofuran; hexane / 4.5 h / -78 &deg;C<br />10.1: 85 percent / CuCN / tetrahydrofuran / 3.5 h / 10 &deg;C<br />11.1: TBAF / tetrahydrofuran / 5 h / 40 - 50 &deg;C<br />11.2: 62 percent / benzene; CHCl₃ / Heating<br /> <br /> &nbsp;