2-[tert-butyl(dimethyl)silyl]oxy-2-cyclopropylethanol

Conditions: temp:0.00; pressure:0.00; stir:; See reaction.notes.procedure_details.

Procedure: To a solution of 2,4,6-trichloro-pyrimidin-5-ol (250 mg, 1.25 mmol), 2-(tert-butyl-dimethyl-silanyloxy)-2-cyclopropyl-ethanol (407 mg, 1.88 mmol) and triphenylphosphine (493 mg, 1.88 mmol) in THF (12 mL) was added DIAD (370 μL, 1.88 mmol). The reaction mixture was stirred at RT for 18 hours before being concentrated in vacuo. The resultant residue was purified by column chromatography (SiO2, gradient 0-30% ethyl acetate in cyclohexane) to give 5-[2-(tert-Butyl-dimethyl-silanyloxy)-2-cyclopropyl-ethoxy]-2,4,6-trichloro-pyrimidine as a viscous yellow oil (411 mg, 83%). 1H NMR (400 MHz, CDCl3): δ 4.14 (1H, dd, J=8.83, 6.02 Hz), 3.99 (1H, dd, J=8.82, 4.21 Hz), 3.60-3.53 (1H, m), 1.13-1.03 (1H, m), 0.89 (9H, s), 0.56-0.50 (2H, m), 0.46-0.28 (2H, m), 0.10 (3H, s), 0.07 (3H, s). before being concentrated in vacuo The resultant residue was purified by column chromatography (SiO2, gradient 0-30% ethyl acetate in cyclohexane)

Conditions: temp:-78.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

Procedure: To a solution of (tert-butyl-dimethyl-silanyloxy)-cyclopropyl-acetic acid methyl ester (1.66 g, 6.79 mmol) in DCM (27 mL) at −78° C. under a nitrogen atmosphere was added DIBAL-H (20.37 mL, 20.37 mmol, 1.0M in toluene) dropwise. The reaction mixture was stirred at −78° C. for 2.5 hours then at 0° C. for 1 hour before being quenched with Rochelle's salt (30 mL, 1M aqueous solution). The mixture was extracted with ethyl acetate (3×30 mL) before the combined organic phases were dried (Na2SO4) and concentrated in vacuo giving 2-(tert-Butyl-dimethyl-silanyloxy)-2-cyclopropyl-ethanol as a pale orange oil (764 mg, 52%). 1H NMR (400 MHz, CDCl3): δ 3.66-3.49 (2H, m), 3.09 (1H, ddd, J=7.96, 6.40, 3.80 Hz), 1.96 (1H, dd, J=7.43, 5.46 Hz), 0.91 (9H, s), 0.91-0.82 (1H, m), 0.57-0.43 (2H, m), 0.34-0.24 (1H, m), 0.23-0.14 (1H, m), 0.11 (3H, s), 0.07 (3H, s). at 0° C. for 1 hour before being quenched with Rochelle's salt (30 mL, 1M aqueous solution) The mixture was extracted with ethyl acetate (3×30 mL) before the combined organic phases were dried (Na2SO4) concentrated in vacuo

Conditions: temp:0.00; pressure:0.00; stir:; See reaction.notes.procedure_details.

Procedure: To a solution of 2,4,6-trichloro-pyrimidin-5-ol (250 mg, 1.25 mmol), 2-(tert-butyl-dimethyl-silanyloxy)-2-cyclopropyl-ethanol (407 mg, 1.88 mmol) and triphenylphosphine (493 mg, 1.88 mmol) in THF (12 mL) was added DIAD (370 μL, 1.88 mmol). The reaction mixture was stirred at RT for 18 hours before being concentrated in vacuo. The resultant residue was purified by column chromatography (SiO2, gradient 0-30% ethyl acetate in cyclohexane) to give 5-[2-(tert-Butyl-dimethyl-silanyloxy)-2-cyclopropyl-ethoxy]-2,4,6-trichloro-pyrimidine as a viscous yellow oil (411 mg, 83%). 1H NMR (400 MHz, CDCl3): δ 4.14 (1H, dd, J=8.83, 6.02 Hz), 3.99 (1H, dd, J=8.82, 4.21 Hz), 3.60-3.53 (1H, m), 1.13-1.03 (1H, m), 0.89 (9H, s), 0.56-0.50 (2H, m), 0.46-0.28 (2H, m), 0.10 (3H, s), 0.07 (3H, s). before being concentrated in vacuo The resultant residue was purified by column chromatography (SiO2, gradient 0-30% ethyl acetate in cyclohexane)

Conditions: temp:-78.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

Procedure: To a solution of (tert-butyl-dimethyl-silanyloxy)-cyclopropyl-acetic acid methyl ester (1.66 g, 6.79 mmol) in DCM (27 mL) at −78° C. under a nitrogen atmosphere was added DIBAL-H (20.37 mL, 20.37 mmol, 1.0M in toluene) dropwise. The reaction mixture was stirred at −78° C. for 2.5 hours then at 0° C. for 1 hour before being quenched with Rochelle's salt (30 mL, 1M aqueous solution). The mixture was extracted with ethyl acetate (3×30 mL) before the combined organic phases were dried (Na2SO4) and concentrated in vacuo giving 2-(tert-Butyl-dimethyl-silanyloxy)-2-cyclopropyl-ethanol as a pale orange oil (764 mg, 52%). 1H NMR (400 MHz, CDCl3): δ 3.66-3.49 (2H, m), 3.09 (1H, ddd, J=7.96, 6.40, 3.80 Hz), 1.96 (1H, dd, J=7.43, 5.46 Hz), 0.91 (9H, s), 0.91-0.82 (1H, m), 0.57-0.43 (2H, m), 0.34-0.24 (1H, m), 0.23-0.14 (1H, m), 0.11 (3H, s), 0.07 (3H, s). at 0° C. for 1 hour before being quenched with Rochelle's salt (30 mL, 1M aqueous solution) The mixture was extracted with ethyl acetate (3×30 mL) before the combined organic phases were dried (Na2SO4) concentrated in vacuo