(2S)-2-[tert-butyl(dimethyl)silyl]oxypropan-1-ol

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

Procedure: Diisobutylaluminum hydride (1M in DCM) (41.4 mL, 41.42 mmol) was added dropwise to a stirred solution of (S)-ethyl 2-(tert-butyldimethylsilyloxy)propanoate (CAS no. 106513-42-2) (5 mL, 18.83 mmol) in diethyl ether (25 mL) at ˜78° C. under nitrogen. The resulting mixture was stirred at r.t. for 2 hours. The reaction mixture was carefully quenched with 20% Rochelle's solution (>100 ml) and at −78° C. and allowed to warm to r.t. After 2 hours of vigourous stirring the mixture was extracted with Et2O ×2, the organic layer was dried (MgSO4), filtered and evaporated to afford colourless liquid, (S)-2-(tert-butyldimethylsilyloxy)propan-1-ol (3.50 g, 98%). 1H NMR (400 MHz, CDCl3) δ 0.00 (6H, s), 0.81 (9H, s), 1.03 (3H, d), 1.71-1.90 (1H, m), 3.24-3.33 (1H, m), 3.35-3.44 (1H, m), 3.78-3.87 (1H, m). at ˜78° C. The reaction mixture was carefully quenched with 20% Rochelle's solution (>100 ml) and at −78° C. to warm to r.t After 2 hours of vigourous stirring the mixture was extracted with Et2O ×2 the organic layer was dried (MgSO4) filtered evaporated

Conditions: temp:80.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

Procedure: Magnesium trifluoromethanesulfonate (1.779 g, 5.52 mmol) was added in one portion to (S)-2-(tert-butyldimethylsilyloxy)propan-1-ol (Intermediate AS4) (4.2 g, 22.06 mmol) and (S)-methyl oxirane-2-carboxylate (2.252 g, 22.06 mmol) in EtOAc (25 mL). The resulting suspension was stirred at 80° C. for 24 hours. A further 1.5 g of the oxirane was added and the reaction stirred for 4 days. The reaction mixture was diluted with EtOAc, filtered through celite and evaporated to dryness. The crude product was purified by flash silica chromatography, elution gradient 0 to 30% EtOAc in isohexane to afford the product (2.70 g, 41.8%). 1H NMR (400 MHz, CDCl3) δ 0.00 (6H, d), 0.82 (9H, s), 1.06 (3H, d), 3.04 (1H, d), 3.25-3.39 (2H, m), 3.65-3.78 (5H, m), 3.83-3.92 (1H, m), 4.19-4.27 (1H, m) the reaction stirred for 4 days filtered through celite evaporated to dryness The crude product was purified by flash silica chromatography, elution gradient 0 to 30% EtOAc in isohexane

Conditions: temp:0.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

Procedure: To a solution of 17A (1.33 g, 6.09 mmol) in THF (20 mL) at 0° C., was added lithium borohydride (0.531 g, 24.36 mmol). The resultant suspension was stirred at rt for 7 h. The reaction was cooled to 0° C., then was quenched with sat. NH4Cl (5 mL). The mixture was diluted with H2O and hexanes. The reaction mixture was acidified with 1 N HCl, then was extracted with hexanes (3×). The combined organic phase was washed with brine, dried (Na2SO4), and concentrated. The crude product was purified by flash chromatography (0 to 60% ethyl acetate/hexanes) to give 17B (980 mg, 5.15 mmol, 85% yield) as a colorless oil. MS (ESI) m/z: 191.2 [M+1]+. 1H NMR (400 MHz, chloroform-d) δ ppm 3.87-3.96 (m, J=6.3, 6.3, 6.3, 6.3, 3.6 Hz, 1H) 3.51 (ddd, J=11.0, 7.7, 3.6 Hz, 1 H) 3.37 (ddd, J=11.1, 6.3, 5.1 Hz, 1H) 1.93 (dd, J=7.8, 5.3 Hz, 1H) 1.12 (d, J=6.3 Hz, 3H) 0.90 (s, 9H) 0.09 (s, 6H). was quenched with sat. NH4Cl (5 mL) The mixture was diluted with H2O and hexanes was extracted with hexanes (3×) The combined organic phase was washed with brine dried (Na2SO4) concentrated The crude product was purified by flash chromatography (0 to 60% ethyl acetate/hexanes)

Conditions: temp:0.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

Procedure: To a solution of 17A (1.33 g, 6.09 mmol) in THF (20 mL) at 0° C., was added lithium borohydride (0.531 g, 24.36 mmol). The resultant suspension was stirred at rt for 7 h. The reaction was cooled to 0° C., then was quenched with sat. NH4Cl (5 mL). The mixture was diluted with H2O and hexanes. The reaction mixture was acidified with 1 N HCl, then was extracted with hexanes (3×). The combined organic phase was washed with brine, dried (Na2SO4), and concentrated. The crude product was purified by flash chromatography (0 to 60% ethyl acetate/hexanes) to give 17B (980 mg, 5.15 mmol, 85% yield) as a colorless oil. MS (ESI) m/z: 191.2 [M+1]+. 1H NMR (400 MHz, chloroform-d) δ ppm 3.87-3.96 (m, J=6.3, 6.3, 6.3, 6.3, 3.6 Hz, 1H) 3.51 (ddd, J=11.0, 7.7, 3.6 Hz, 1 H) 3.37 (ddd, J=11.1, 6.3, 5.1 Hz, 1H) 1.93 (dd, J=7.8, 5.3 Hz, 1H) 1.12 (d, J=6.3 Hz, 3H) 0.90 (s, 9H) 0.09 (s, 6H). was quenched with sat. NH4Cl (5 mL) The mixture was diluted with H2O and hexanes was extracted with hexanes (3×) The combined organic phase was washed with brine dried (Na2SO4) concentrated The crude product was purified by flash chromatography (0 to 60% ethyl acetate/hexanes)

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

Procedure: To a suspension of (S)-2-(tert-butyl-dimethyl-silanyloxy)-propan-1-ol (53.0 g, 0.28 mol), N-hydroxyphthalimide (47.0 g, 0.29 mol) and triphenylphosphine (77.9 g, 0.30 mol) in THF (200 ml) at 0° C. was added dropwise DIAD (56.8 ml, 0.29 mol). During the addition the reagents dissolved and the solution turned a dark red colour before fading to pale yellow colour on completion of the addition. The reaction mixture was stirred and allowed to warm to room temperature overnight. The reaction mixture was concentrated in vacuo and the resultant residue re-dissolved in diethyl ether. The suspension was filtered and the filtrate was concentrated in vacuo to yield the crude title compound as a pale yellow oil. The material was used without further purification in the subsequent step. During the addition the reagents dissolved before fading to pale yellow colour on completion of the addition The reaction mixture was concentrated in vacuo the resultant residue re-dissolved in diethyl ether The suspension was filtered the filtrate was concentrated in vacuo

Conditions: temp:0.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

Procedure: A 2M solution of LiBH4 (2.77 g, 0.13 mol) in THF (60 mL) was added dropwise to a solution of (S)-2-(tert-butyl-dimethyl-silanyloxy)-propionic acid ethyl ester (22.75 g, 0.10 mol) and methanol (5.15 mL, 0.13 mol) in diethyl ether (500 mL) at 0° C. The reaction mixture was stirred at 0° C. for 1 hour and then at room temperature for 1.5 hours before cooling to 0° C. and carefully quenching with water. The reaction mixture was filtered and the filtrate extracted with diethyl ether (2×50 mL), the combined organic extracts were washed with brine, dried (MgSO4) and concentrated in vacuo to give the title product as a colourless oil (18.2 g, 97%). 1H NMR (CDCl3, 400 MHz) 3.86-3.77 (1H, m), 3.45-3.37 (1H, m), 3.31-3.22 (1H, m), 1.96-1.85 (1H, m), 1.03 (3H, d, J=6.23 Hz), 0.81 (9H, s), 0.00 (6H, s). at room temperature for 1.5 hours before cooling to 0° C. carefully quenching with water The reaction mixture was filtered the filtrate extracted with diethyl ether (2×50 mL) the combined organic extracts were washed with brine dried (MgSO4) concentrated in vacuo

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

Procedure: Diisobutylaluminum hydride (1M in DCM) (41.4 mL, 41.42 mmol) was added dropwise to a stirred solution of (S)-ethyl 2-(tert-butyldimethylsilyloxy)propanoate (CAS no. 106513-42-2) (5 mL, 18.83 mmol) in diethyl ether (25 mL) at ˜78° C. under nitrogen. The resulting mixture was stirred at r.t. for 2 hours. The reaction mixture was carefully quenched with 20% Rochelle's solution (>100 ml) and at −78° C. and allowed to warm to r.t. After 2 hours of vigourous stirring the mixture was extracted with Et2O ×2, the organic layer was dried (MgSO4), filtered and evaporated to afford colourless liquid, (S)-2-(tert-butyldimethylsilyloxy)propan-1-ol (3.50 g, 98%). 1H NMR (400 MHz, CDCl3) δ 0.00 (6H, s), 0.81 (9H, s), 1.03 (3H, d), 1.71-1.90 (1H, m), 3.24-3.33 (1H, m), 3.35-3.44 (1H, m), 3.78-3.87 (1H, m). at ˜78° C. The reaction mixture was carefully quenched with 20% Rochelle's solution (>100 ml) and at −78° C. to warm to r.t After 2 hours of vigourous stirring the mixture was extracted with Et2O ×2 the organic layer was dried (MgSO4) filtered evaporated

Conditions: temp:80.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

Procedure: Magnesium trifluoromethanesulfonate (1.779 g, 5.52 mmol) was added in one portion to (S)-2-(tert-butyldimethylsilyloxy)propan-1-ol (Intermediate AS4) (4.2 g, 22.06 mmol) and (S)-methyl oxirane-2-carboxylate (2.252 g, 22.06 mmol) in EtOAc (25 mL). The resulting suspension was stirred at 80° C. for 24 hours. A further 1.5 g of the oxirane was added and the reaction stirred for 4 days. The reaction mixture was diluted with EtOAc, filtered through celite and evaporated to dryness. The crude product was purified by flash silica chromatography, elution gradient 0 to 30% EtOAc in isohexane to afford the product (2.70 g, 41.8%). 1H NMR (400 MHz, CDCl3) δ 0.00 (6H, d), 0.82 (9H, s), 1.06 (3H, d), 3.04 (1H, d), 3.25-3.39 (2H, m), 3.65-3.78 (5H, m), 3.83-3.92 (1H, m), 4.19-4.27 (1H, m) the reaction stirred for 4 days filtered through celite evaporated to dryness The crude product was purified by flash silica chromatography, elution gradient 0 to 30% EtOAc in isohexane

Conditions: temp:0.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

Procedure: To a solution of 17A (1.33 g, 6.09 mmol) in THF (20 mL) at 0° C., was added lithium borohydride (0.531 g, 24.36 mmol). The resultant suspension was stirred at rt for 7 h. The reaction was cooled to 0° C., then was quenched with sat. NH4Cl (5 mL). The mixture was diluted with H2O and hexanes. The reaction mixture was acidified with 1 N HCl, then was extracted with hexanes (3×). The combined organic phase was washed with brine, dried (Na2SO4), and concentrated. The crude product was purified by flash chromatography (0 to 60% ethyl acetate/hexanes) to give 17B (980 mg, 5.15 mmol, 85% yield) as a colorless oil. MS (ESI) m/z: 191.2 [M+1]+. 1H NMR (400 MHz, chloroform-d) δ ppm 3.87-3.96 (m, J=6.3, 6.3, 6.3, 6.3, 3.6 Hz, 1H) 3.51 (ddd, J=11.0, 7.7, 3.6 Hz, 1 H) 3.37 (ddd, J=11.1, 6.3, 5.1 Hz, 1H) 1.93 (dd, J=7.8, 5.3 Hz, 1H) 1.12 (d, J=6.3 Hz, 3H) 0.90 (s, 9H) 0.09 (s, 6H). was quenched with sat. NH4Cl (5 mL) The mixture was diluted with H2O and hexanes was extracted with hexanes (3×) The combined organic phase was washed with brine dried (Na2SO4) concentrated The crude product was purified by flash chromatography (0 to 60% ethyl acetate/hexanes)