3-(benzyloxy)-2,2-diMethylpropan-1-ol

Into a 10-L 4-neck round-bottom flask, was placed 2, 2-dimethylpropane-1, 3-diol (200 g, 1920 mmol), toluene (1 L), 50percent KOH (aq. solution, 1L), n-Bu4NI (36 g, 97 mmol). Then (bromomethyl)benzene (328 g, 1920 mmol, 1.00 equiv.) was added at 0 °C. The resulting solution was stirred at room temperature for 16 h. The reaction was then quenched by the addition of 1 L of ice-water. The resulting solution was extracted with 2x4 L of ethyl acetate. The combined organic layer was washed with 2x4 L of brine, dried over anhydrous sodium sulfate and concentrated under vacuum. The crude product was purified by silica gel column chromatography to afford the title compound as light yellow oil (77percent). LCMS:mlz=195.0 [M+1]. ‘H-NMR (300 MHz, CDC13) ö: 7.37-7.25 (m, 5H), 4.47 (m, 3H), 3.18 (d, 1=6.4Hz, 4H), 0.82 (s, 6H).General procedure: The diol (48 mmol, 1 eq) wasdissolved into DMF (120 mL) under argon. At 0°C NaH (1.1 eq, 60percent in mineral oil) was added inone portion and the mixture was stirred at 0°C during 45 min. BnBr (0.97 eq) was added dropwise, the mixture was allowed to warm at room temperature and stirred overnight. The reaction wasquenched with saturated NH4Cl solution (20 mL) and then diluted with water. The crude mixturewas extracted with Et2O and the organic layer was washed with brine, dried over anhydrous MgSO4, filtered and concentrated in vacuo. Benzylated compound was then purified by flashchromatography on silica gel.Step A: [00319] Into a 250-mL round-bottom flask, was placed 2, 2-dimethylpropane-1, 3-diol (10.4 g, 99.86 mmol) and N, N-dimethylformamide (100 mL). This was followed by the addition of 60percent sodium hydride (4 g, 100.00 mmol), in portions at 0°C. To this was added (bromomethyl)benzene (13.68 g, 79.98 mmol) at 0°C. The resulting solution was stuffed for 12 h at room temperature and then diluted with 200 mL of NH4C1 (sat. aq). The resulting solution was extracted with 2x200 mL of ethyl acetate and the organic layers were combined and dried over anhydrous sodium sulfate and concentrated under vacuum. The residue was purified by silica gel column with ethyl acetate/petroleum ether (1:10) to obtain 12 g (62percent) of 3-(benzyloxy)-2, 2-dimethylpropan-1-ol as light yellow oil. ‘H NMR (300 MHz, DMSOd 6): 7.43-7.24 (m, 5H), 4.51-4.41 (m, 3H), 3.25-3.15 (m, 4H), 0.84 (s, 6H) ppm.[00509] 2, 2-Dimethylpropane-l, 3-diol 159 (4.24 g, 40 mmol) was dissolved in 120 mL of THF. To this mixture, was added NaH (1.92 g, 48 mmol, 60percent in mineral oil) at 0 °C under nitrogen atmosphere. After stirring at 0 °C for 30 min, benzyl bromide (6.84 g, 40 mmol) was added to this mixture, and the resulting mixture was stirred at room temperature overnight. The reaction mixture was then transferred into iced water and extracted with ethyl acetate (50 mL X 3). The combined organic layers were washed with brine, dried over anhydrous NaA solution of 2, 2-dimethyl-propane-l, 3-diol (25.85 g, 248 mmol) in dioxane (400 mL) was cooled to 0°C. Potassium tert-butoxide (30 g, 267 mmol) was added portionwise to the cooled solution. The resulting mixture was stirred at room temperature for 1 h. (Bromomethyl)benzene (29.5 mL, 248 mmol) was added dropwise via addition funnel. The mixture was heated to 90°C and stirred for 4 h. The resulting mixture was concentrated in vacuo. The resulting residue was partitioned between water (200 mL) and ethyl acetate (200 mL) and extracted with ethyl acetate (3x200 mL). The organics were combined, washed with brine (100 mL), dried on sodium sulfate, and concentrated in vacuo. The crude material was purified by column chromatography (Si0Sodium hydride (2.50 g, 105.62 mmol, 60percent in mineral oil) was suspended in dry DMF (150 ml) at 0° C. and a solution of 2, 2-dimethylpropane-1, 3-diol (10.0 g, 96.02 mmol) in DMF (50.0 ml) was added dropwise. Methyl 3-(benzyloxy)-2, 2-dimethylpropanoate (8a) (2.91 g, 13.1 mmol) was dissolved in THF and was cooled to -78 °C. LiAlH4 (14.4 mL, 14.4 mmol, 1 M) was added slowly via syringe to the solution. After stirring for 15 min at -78 °C, the cooling bath was removed and was replaced with an ice-water bath. The reaction mixture was stirred at 0 °C for 30 min. Excess LiAlH4 was quenched with ethyl acetate (3 mL). The mixture was warmed to r.t. and 0.55 mL water followed by 0.55 mL NaOH (15percent aq solution) followed by 1.65 mL water was added to the mixture and the resulting precipitate was removed by filtration through a pad of Celite with ethyl acetate rinsing. The filtrate was transferred to a separatory funnel containing saturated aqueous NaHCO3 solution (50 mL) and the aqueous layer was extracted with ethyl acetate (3 x 50 mL). The combined organic layers were washed with brine (50 mL), dried over MgSO4, filtered, and concentrated. The product was purified by column chromatography on silica gel (20percent → 25percent ethyl acetate in hexanes) to afford 3-(benzyloxy)-2, 2-dimethylpropan-1-ol (8b) (2.40 g, 94percent yield) as a colorless oil: 1H NMR (400 MHz, CHLOROFORM-d) δ 7.39 - 7.25 (m, 5H), 4.50 (s, 2H), 3.45 (d, J=5.8 Hz, 2H), 3.31 (s, 2H), 0.92 (s, 6H); MS (ESI) m/e 195.2 [(M+H)+, calcd for C12H19O2 195.1].

Molecular Weight:194.27
XLogP3:2.1
Hydrogen Bond Donor Count:1
Hydrogen Bond Acceptor Count:2
Rotatable Bond Count:5
Exact Mass:194.130679813
Monoisotopic Mass:194.130679813
Topological Polar Surface Area:29.5
Heavy Atom Count:14
Complexity:148
Covalently-Bonded Unit Count:1
Compound Is Canonicalized:Yes