3-methylbutane-1,3-diol

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

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

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

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

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

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

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

Procedure: The dibromo-intermediate from Example 471B was reacted according to the procedure described in Example 194B, substituting 3-methyl-1,3-butanediol in place of methanol, to selectively react at the 4-position and provide the title intermediate. to selectively react at the 4-position

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

Procedure: A solution of 16 mL 3-methylbutane-1,3-diol in 10 mL methylene chloride with a catalytic amount of 4-dimethylpyridine was cooled to 0° C. Acetic anhydride (4.084 g, 40 mmol) was then added drop wise and the solution was stirred for 5 hours. An additional 10 mL of methylene chloride was added and the solution was washed with 10% aqueous ammonium chloride (2×20 mL), 5% sodium carbonate (2×20 mL) and brine (1×20 mL), dried over sodium sulfate and evaporated to dryness to yield a clear, yellow liquid. (2.402 g) 1H NMR (400 MHz, CDCl3): δ 1.24 (s, 6H), 1.56 (b, 1H), 1.80-1.83 (t, J=6.8, 2H), 2.02 (s, 3H), 4.22 (t, J=6.9, 2H). the solution was washed with 10% aqueous ammonium chloride (2×20 mL), 5% sodium carbonate (2×20 mL) and brine (1×20 mL) dried over sodium sulfate evaporated to dryness to yield a clear, yellow liquid

Conditions: temp:2.51; pressure:0.00; stir:; See reaction.notes.procedure_details.

Procedure: 3-Methylbutane-1,3-diol (42 mg, 0.4 mmol) in THF (1 mL) was treated with NaH (60%) (16 mg, 0.4 mmol) at room temperature for 20 min. To the above mixture, which was cooled to 0-5° C., was added the product from Example 20B (80 mg, 0.2 mmol) in THF (1 mL). After 20 min. the reaction mixture was quenched with saturated aqueous NaHCO3 (20 mL) and extracted with ethyl acetate (2×30 mL). The combined organic extracts were dried over anhydrous Na2SO4, filtered, and concentrated under reduced pressure. The residue was purified by column chromatography using an Analogix® Intelliflash280™ (SiO2, 0-100% ethyl acetate in hexanes) to afford 87 mg (90%) of the title compound. 1H NMR (500 MHz, CDCl3) δ ppm 1.04 (t, J=7.32 Hz, 3H) 1.36 (s, 6H) 1.47-1.55 (m, 2H) 1.88-1.96 (m, 2H) 2.13 (t, J=5.80 Hz, 2H) 4.35 (t, J=5.80 Hz, 2H) 4.54 (t, J=7.63 Hz, 2H) 5.12 (brs, 1H) 7.11 (d, J=8.54 Hz, 1H) 7.61 (d, J=5.19 Hz, 1H) 7.74 (dd, J=8.54, 2.14 Hz, 1H) 8.49 (d, J=5.19 Hz, 1H) 8.68 (s, 1H) 8.72 (s, 1H); MS (ESI+) m/z 482 (M+H)+. After 20 min. the reaction mixture was quenched with saturated aqueous NaHCO3 (20 mL) extracted with ethyl acetate (2×30 mL) The combined organic extracts were dried over anhydrous Na2SO4 filtered concentrated under reduced pressure The residue was purified by column chromatography

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

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

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

Procedure: To a solution of 3-methylbutane-1,3-diol (2.5 mL) in dichloromethane (30 mL) and pyridine (2.1 mL) is added at 0° C. p-toluene-sulfonylchloride (4.6 g) in portions. The mixture is stirred for 12 hours at room temperature, diluted with dichloromethane and washed with 1 M aqueous HCl solution and brine. After drying (MgSO4) the solvent is evaporated and the product is purified by chromatography on silica gel (cyclohexane/ethyl acetate 90:10→70:30) to give the title compound. Yield: 3.2 g; Mass spectrum (ESI+): m/z=276 [M+NH4]+. washed with 1 M aqueous HCl solution and brine After drying (MgSO4) the solvent is evaporated the product is purified by chromatography on silica gel (cyclohexane/ethyl acetate 90:10→70:30)