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

Conditions: temp:10.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

Procedure: Magnesium trifluoromethanesulfonate (1.165 g, 3.61 mmol) was added in one portion to (S)-methyl oxirane-2-carboxylate (1.475 g, 14.45 mmol) and (R)-1-(tert-butyldimethylsilyloxy)propan-2-ol (CAS no. 136918-07-5) (2.75 g, 14.45 mmol) cooled to 10° C. The resulting suspension was stirred at 10° C. for 10 minutes and then warmed to 45° C. and stirred for 2 days. The crude product was purified by flash silica chromatography, eluting with 0 to 30% EtOAc in isohexane to afford the product (1.680 g, 39.8%). 1H NMR (400 MHz, DMSO) δ0.00 (s, 6H), 0.83 (s, 9H), 0.98 (d, 3H), 3.35-3.45 (m, 2H), 3.47-3.65 (m, 3H), 3.66 (s, 3H), 4.09-4.15 (m, 1H), 5.37 (d, 1H). warmed to 45° C. stirred for 2 days The crude product was purified by flash silica chromatography eluting with 0 to 30% EtOAc in isohexane

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

Procedure: tert-Butyl(dimethyl)silyl chloride (5.90 g, 39.5 mmol) was added to a solution of (2R)-propane-1,2-diol (3.00 g, 39.5 mmol) in DCM (100 mL) followed by diisopropylethylamine (7.10 g, 55.3 mmol) and the reaction was stirred under argon for 72 h. The reaction was diluted with diethyl ether (500 mL) and water (140 mL) and the organic layer was separated then dried (MgSO4), filtered and evaporated. Purification by column chromatography, eluting with 1:15 to 1:10 ethyl acetate:hexane, afforded the title compound as a colourless oil (6.00 g, 80%). the organic layer was separated then dried (MgSO4) filtered evaporated Purification by column chromatography eluting with 1:15 to 1:10 ethyl acetate

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

Procedure: (2R)-1-{[(1,1-Dimethylethyl)(dimethyl)silyl]oxy}propan-2-ol (3.31 g, 17.4 mmol) was added to a solution of methyl 3-hydroxy-5-{[phenylmethyl]oxy}benzoate (3.00 g, 11.6 mmol) in THF (50 mL) at 0° C. followed by addition of triphenylphosphine (4.57 g, 17.4 mmol) then DIAD (3.43 mL, 17.4 mmol) and the reaction was warmed to RT and stirred for 16 h. The reaction was quenched with water (100 mL) and diethyl ether (400 mL) and the organic layer was separated then dried (MgSO4) and evaporated. Purification by column chromatography, eluting with 1:15 to 1:5 ethyl acetate:hexane, afforded the title compound as a colourless oil (4.00 g, 80%). The reaction was quenched with water (100 mL) and diethyl ether (400 mL) the organic layer was separated then dried (MgSO4) evaporated Purification by column chromatography eluting with 1:15 to 1:5 ethyl acetate

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

Procedure: To a solution of 27B (400 mg, 1.197 mmol), 33A (251 mg, 1.316 mmol) and triphenylphosphine (345 mg, 1.316 mmol) in THF (10 mL) at 0° C., was added DIAD (0.256 mL, 1.316 mmol) dropwise. The reaction mixture was allowed to slowly warm to rt and stirred for 16 h, then was concentrated. The crude product was purified by flash chromatography (0 to 40% ethyl acetate/hexanes) to give 33B (577 mg, 1.139 mmol, 95% yield) as colorless oil. MS (ESI) m/z: 507.1[M+1]+. 1H NMR (400 MHz, chloroform-d) δ ppm 7.78-7.94 (2H, m) 7.27-7.43 (5H, m) 5.17 (2H, d, J=20.1 Hz) 4.46-4.74 (3H, m) 3.65-3.81 (2H, m) 2.97 (3H, d, J=15.8 Hz) 1.31 (3H, t, J=7.0 Hz) 0.81 (9H, d, J=7.0 Hz) −0.05-0.04 (6H, m) rotamers. was concentrated The crude product was purified by flash chromatography (0 to 40% ethyl acetate/hexanes)

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

Procedure: To a solution of 27B (400 mg, 1.197 mmol), 33A (251 mg, 1.316 mmol) and triphenylphosphine (345 mg, 1.316 mmol) in THF (10 mL) at 0° C., was added DIAD (0.256 mL, 1.316 mmol) dropwise. The reaction mixture was allowed to slowly warm to rt and stirred for 16 h, then was concentrated. The crude product was purified by flash chromatography (0 to 40% ethyl acetate/hexanes) to give 33B (577 mg, 1.139 mmol, 95% yield) as colorless oil. MS (ESI) m/z: 507.1[M+1]+. 1H NMR (400 MHz, chloroform-d) δ ppm 7.78-7.94 (2H, m) 7.27-7.43 (5H, m) 5.17 (2H, d, J=20.1 Hz) 4.46-4.74 (3H, m) 3.65-3.81 (2H, m) 2.97 (3H, d, J=15.8 Hz) 1.31 (3H, t, J=7.0 Hz) 0.81 (9H, d, J=7.0 Hz) −0.05-0.04 (6H, m) rotamers. was concentrated The crude product was purified by flash chromatography (0 to 40% ethyl acetate/hexanes)

Conditions: temp:25.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

Procedure: To a solution of (s)-(+)-1,2-propanediol (2.0 g, 26.3 mmol) in DMF (5 mL) was added TBS-Cl (5.94 g, 39.4 mmol) and imidazole (2.147 g, 31.5 mmol). The reaction was stirred at 25° C. for 18 h. The reaction mixture was partitioned between ethyl acetate and sat. ammonium chloride. The organic phase was washed with sat ammonium chloride and brine, dried (MgSO4) and concentrated in vacuo. The crude product was purified by flash chromatography to give 33A (4.0 g, 80% yield) as a colorless oil. The reaction mixture was partitioned between ethyl acetate and sat. ammonium chloride The organic phase was washed with sat ammonium chloride and brine dried (MgSO4) concentrated in vacuo The crude product was purified by flash chromatography

Conditions: temp:10.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

Procedure: Magnesium trifluoromethanesulfonate (1.165 g, 3.61 mmol) was added in one portion to (S)-methyl oxirane-2-carboxylate (1.475 g, 14.45 mmol) and (R)-1-(tert-butyldimethylsilyloxy)propan-2-ol (CAS no. 136918-07-5) (2.75 g, 14.45 mmol) cooled to 10° C. The resulting suspension was stirred at 10° C. for 10 minutes and then warmed to 45° C. and stirred for 2 days. The crude product was purified by flash silica chromatography, eluting with 0 to 30% EtOAc in isohexane to afford the product (1.680 g, 39.8%). 1H NMR (400 MHz, DMSO) δ0.00 (s, 6H), 0.83 (s, 9H), 0.98 (d, 3H), 3.35-3.45 (m, 2H), 3.47-3.65 (m, 3H), 3.66 (s, 3H), 4.09-4.15 (m, 1H), 5.37 (d, 1H). warmed to 45° C. stirred for 2 days The crude product was purified by flash silica chromatography eluting with 0 to 30% EtOAc in isohexane

Conditions: temp:10.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

Procedure: Magnesium trifluoromethanesulfonate (1.165 g, 3.61 mmol) was added in one portion to (S)-methyl oxirane-2-carboxylate (1.475 g, 14.45 mmol) and (R)-1-(tert-butyldimethylsilyloxy)propan-2-ol (CAS no. 136918-07-5) (2.75 g, 14.45 mmol) cooled to 10° C. The resulting suspension was stirred at 10° C. for 10 minutes and then warmed to 45° C. and stirred for 2 days. The crude product was purified by flash silica chromatography, eluting with 0 to 30% EtOAc in isohexane to afford the product (1.680 g, 39.8%). 1H NMR (400 MHz, DMSO) δ0.00 (s, 6H), 0.83 (s, 9H), 0.98 (d, 3H), 3.35-3.45 (m, 2H), 3.47-3.65 (m, 3H), 3.66 (s, 3H), 4.09-4.15 (m, 1H), 5.37 (d, 1H). warmed to 45° C. stirred for 2 days The crude product was purified by flash silica chromatography eluting with 0 to 30% EtOAc in isohexane

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

Procedure: tert-Butyl(dimethyl)silyl chloride (5.90 g, 39.5 mmol) was added to a solution of (2R)-propane-1,2-diol (3.00 g, 39.5 mmol) in DCM (100 mL) followed by diisopropylethylamine (7.10 g, 55.3 mmol) and the reaction was stirred under argon for 72 h. The reaction was diluted with diethyl ether (500 mL) and water (140 mL) and the organic layer was separated then dried (MgSO4), filtered and evaporated. Purification by column chromatography, eluting with 1:15 to 1:10 ethyl acetate:hexane, afforded the title compound as a colourless oil (6.00 g, 80%). the organic layer was separated then dried (MgSO4) filtered evaporated Purification by column chromatography eluting with 1:15 to 1:10 ethyl acetate

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

Procedure: tert-Butyl(dimethyl)silyl chloride (5.90 g, 39.5 mmol) was added to a solution of (2R)-propane-1,2-diol (3.00 g, 39.5 mmol) in DCM (100 mL) followed by diisopropylethylamine (7.10 g, 55.3 mmol) and the reaction was stirred under argon for 72 h. The reaction was diluted with diethyl ether (500 mL) and water (140 mL) and the organic layer was separated then dried (MgSO4), filtered and evaporated. Purification by column chromatography, eluting with 1:15 to 1:10 ethyl acetate:hexane, afforded the title compound as a colourless oil (6.00 g, 80%). the organic layer was separated then dried (MgSO4) filtered evaporated Purification by column chromatography eluting with 1:15 to 1:10 ethyl acetate

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

Procedure: (2R)-1-{[tert-Butyl(dimethyl)silyl]oxy}propan-2-ol (3.31 g, 17.4 mmol) was added to a solution of methyl 3-hydroxy-5-{[phenylmethyl]oxy}benzoate (3.00 g, 11.6 mmol) in THF (50 mL) at 0° C. followed by addition of triphenylphosphine (4.57 g, 17.4 mmol) then DIAD (3.43 mL, 17.4 mmol) and the reaction was warmed to RT and stirred for 16 h. The reaction was quenched with water (100 mL) and diethyl ether (400 mL) and the organic layer was separated then dried (MgSO4) and evaporated. Purification by column chromatography, eluting with 1:15 to 1:5 ethyl acetate:hexane, afforded the title compound as a colourless oil (4.00 g, 80%). The reaction was quenched with water (100 mL) and diethyl ether (400 mL) the organic layer was separated then dried (MgSO4) evaporated Purification by column chromatography eluting with 1:15 to 1:5 ethyl acetate

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

Procedure: (2R)-1-{[tert-Butyl(dimethyl)silyl]oxy}propan-2-ol (3.31 g, 17.4 mmol) was added to a solution of methyl 3-hydroxy-5-{[phenylmethyl]oxy}benzoate (3.00 g, 11.6 mmol) in THF (50 mL) at 0° C. followed by addition of triphenylphosphine (4.57 g, 17.4 mmol) then DIAD (3.43 mL, 17.4 mmol) and the reaction was warmed to RT and stirred for 16 h. The reaction was quenched with water (100 mL) and diethyl ether (400 mL) and the organic layer was separated then dried (MgSO4) and evaporated. Purification by column chromatography, eluting with 1:15 to 1:5 ethyl acetate:hexane, afforded the title compound as a colourless oil (4.00 g, 80%). The reaction was quenched with water (100 mL) and diethyl ether (400 mL) the organic layer was separated then dried (MgSO4) evaporated Purification by column chromatography eluting with 1:15 to 1:5 ethyl acetate