[1-[[tert-butyl(dimethyl)silyl]oxymethyl]cyclopropyl]methanol

Conditions: temp:0.00; pressure:0.00; stir:

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

Procedure: A solution of [1-({[tert-butyl(dimethyl)silyl]oxy}methyl)cyclopropyl]methanol (Example 34c, 5.37 g) dissolved in DCM (20 mL) was treated with triethylamine (6.92 mL) at 0° C. before adding methanesulfonyl chloride (2.321 mL) under nitrogen. The resulting mixture was stirred at 0° C. for 30 min. The reaction mixture was diluted with water (100 mL), and extracted with DCM (250 mL). The organics were dried (MgSO4), filtered and evaporated. The crude product was purified (SiO2 chromatography, elution 50% isohexane in diethyl ether). Pure fractions were evaporated to dryness to afford the subtitle compound (5.37 g) as an oil. extracted with DCM (250 mL) The organics were dried (MgSO4) filtered evaporated The crude product was purified (SiO2 chromatography, elution 50% isohexane in diethyl ether) Pure fractions were evaporated to dryness

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

Procedure: A solution of [1-({[tert-butyl(dimethyl)silyl]oxy}methyl)cyclopropyl]methanol (Example 34c, 5.37 g) dissolved in DCM (20 mL) was treated with triethylamine (6.92 mL) at 0° C. before adding methanesulfonyl chloride (2.321 mL) under nitrogen. The resulting mixture was stirred at 0° C. for 30 min. The reaction mixture was diluted with water (100 mL), and extracted with DCM (250 mL). The organics were dried (MgSO4), filtered and evaporated. The crude product was purified (SiO2 chromatography, elution 50% isohexane in diethyl ether). Pure fractions were evaporated to dryness to afford the subtitle compound (5.37 g) as an oil. extracted with DCM (250 mL) The organics were dried (MgSO4) filtered evaporated The crude product was purified (SiO2 chromatography, elution 50% isohexane in diethyl ether) Pure fractions were evaporated to dryness

Conditions: temp:20.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

Procedure: A solution of cyclopropane-1,1-diyldimethanol (3.7 g) dissolved in ethylene glycol dimethyl ether (50 mL) was treated with 60% sodium hydride (1.449 g) at 0° C. under nitrogen. The resulting mixture was stirred at 20° C. for 1 h, treated with tert-butylchlorodimethylsilane (5.46 g) and stirred at room temperature overnight. The reaction mixture was diluted with water (250 mL), and extracted with ethyl acetate (2×250 mL). The organic was dried (MgSO4), filtered and evaporated to afford crude product. The crude product was purified (SiO2 chromatography, elution 100% DCM). Pure fractions were evaporated to dryness to afford the subtitle compound (5.50 g) as an oil. stirred at room temperature overnight extracted with ethyl acetate (2×250 mL) The organic was dried (MgSO4) filtered evaporated to afford crude product The crude product was purified (SiO2 chromatography, elution 100% DCM) Pure fractions were evaporated to dryness

Conditions: temp:0.00; pressure:0.00; stir:

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

Procedure: To a round bottom flask was added NaH (1.08 g, 27.0 mmol) and THF (35 mL). The reaction mixture was cooled to about 0° C. and a solution of cyclobutane-1,1-diyldimethanol (3.14 g, 27.0 mmol, prepared according to DE 19735574, Beispiel 8d) in THF (100 mL) was added dropwise. The reaction mixture was stirred for about 30 min and then a solution of tert-butylchlorodimethylsilane (4.07 g, 27.0 mmol) in THF (50 mL) was added dropwise. The reaction mixture was warmed to ambient temperature and the reaction mixture was stirred for about 1 h. The reaction mixture was quenched with the addition of saturated aqueous NaHCO3 (200 mL) and the mixture was extracted with EtOAc (3×200 mL). The organics were combined and washed with brine (500 mL), dried with Na2SO4, filtered and concentrated in vacuo. The crude material was purified by flash chromatography (silica gel 120 g RediSep® column; heptane/EtOAc gradient from 1:0 to 0:1) to give the title compound (3.23 g, 52%). 1H NMR (CDCl3) δ 3.72 (s, 2H), 3.70 (s, 2H), 1.97-1.68 (m, 6H), 0.91 (s, 9H), 0.91 (s, 3H), 0.09 (s, 3H). The reaction mixture was warmed to ambient temperature the reaction mixture was stirred for about 1 h The reaction mixture was quenched with the addition of saturated aqueous NaHCO3 (200 mL) the mixture was extracted with EtOAc (3×200 mL) washed with brine (500 mL) dried with Na2SO4 filtered concentrated in vacuo The crude material was purified by flash chromatography (silica gel 120 g RediSep® column; heptane/EtOAc gradient from 1:0 to 0:1)

Conditions: temp:-70.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

Procedure: To a stirred solution of DMSO (6.9 mL, 0.097 mol) in anhydrous DCM (90 mL) at −70° C. was added oxalyl chloride (4.20 mL, 0.0486 mol). After stirring for 10 min. at −70° C., a solution of [1-({[tert-butyl(dimethyl)silyl]oxy}methyl)cyclopropyl]methanol (7.011 g, 0.03240 mol) in anhydrous DCM (30 mL) was added via cannula. The resulting milky mixture was slowly warmed to −55° C. over 45 min. DIPEA (34.0 mL, 0.194 mol) was added. The resulting mixture was stirred for 5 min. at −55° C., and then the cooling bath was removed and the reaction mixture was allowed to warm to RT. The reaction was then quenched with saturated aqueous NaHCO3 (150 mL) and extracted with DCM (2×). The combined organic layers were washed with brine, dried over magnesium sulfate, filtered and concentrated in vacuo. The resulting residue was purified by Combiflash chromatography eluting with 0-10% EtOAc/hexanes to afford the desired product as a colorless oil (4.558 g, 66% yield). The resulting milky mixture was slowly warmed to −55° C. over 45 min The resulting mixture was stirred for 5 min. at −55° C. the cooling bath was removed to warm to RT The reaction was then quenched with saturated aqueous NaHCO3 (150 mL) extracted with DCM (2×) The combined organic layers were washed with brine dried over magnesium sulfate filtered concentrated in vacuo The resulting residue was purified by Combiflash chromatography eluting with 0-10% EtOAc/hexanes

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

Procedure: 1,1-Bis(hydroxymethyl)cyclopropane (1.0 g, 0.0098 mol), triethylamine (TEA) (2.0 mL, 0.015 mol), and 1H-imidazole (0.13 g, 0.0020 mol) were dissolved in anhydrous DCM (15 mL) and the solution was cooled to 0° C. A solution of tert-butyldimethylsilyl chloride (1.55 g, 0.0103 mol) in DCM (5 mL) was added drop-wise and the resulting mixture was allowed to warm to RT and stirred overnight. The reaction was quenched with saturated aqueous NaHCO3 and extracted with DCM (3×). The organic extract was dried (magnesium sulfate), filtered, and concentrated in vacuo. The crude product was identified by 1H NMR and used in the next step without further purification. to warm to RT The reaction was quenched with saturated aqueous NaHCO3 extracted with DCM (3×) The organic extract was dried (magnesium sulfate) filtered concentrated in vacuo used in the next step without further purification

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

Procedure: A solution of [1-({[tert-butyl(dimethyl)silyl]oxy}methyl)cyclopropyl]methanol (Example 34c, 5.37 g) dissolved in DCM (20 mL) was treated with triethylamine (6.92 mL) at 0° C. before adding methanesulfonyl chloride (2.321 mL) under nitrogen. The resulting mixture was stirred at 0° C. for 30 min. The reaction mixture was diluted with water (100 mL), and extracted with DCM (250 mL). The organics were dried (MgSO4), filtered and evaporated. The crude product was purified (SiO2 chromatography, elution 50% isohexane in diethyl ether). Pure fractions were evaporated to dryness to afford the subtitle compound (5.37 g) as an oil. extracted with DCM (250 mL) The organics were dried (MgSO4) filtered evaporated The crude product was purified (SiO2 chromatography, elution 50% isohexane in diethyl ether) Pure fractions were evaporated to dryness

Conditions: temp:20.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

Procedure: A solution of cyclopropane-1,1-diyldimethanol (3.7 g) dissolved in ethylene glycol dimethyl ether (50 mL) was treated with 60% sodium hydride (1.449 g) at 0° C. under nitrogen. The resulting mixture was stirred at 20° C. for 1 h, treated with tert-butylchlorodimethylsilane (5.46 g) and stirred at room temperature overnight. The reaction mixture was diluted with water (250 mL), and extracted with ethyl acetate (2×250 mL). The organic was dried (MgSO4), filtered and evaporated to afford crude product. The crude product was purified (SiO2 chromatography, elution 100% DCM). Pure fractions were evaporated to dryness to afford the subtitle compound (5.50 g) as an oil. stirred at room temperature overnight extracted with ethyl acetate (2×250 mL) The organic was dried (MgSO4) filtered evaporated to afford crude product The crude product was purified (SiO2 chromatography, elution 100% DCM) Pure fractions were evaporated to dryness