2-cyclohexylethanol

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:

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

Conditions: temp:40.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

Procedure: 0.68 g (17.0 mmol) of sodium hydride (60% oily) was suspended in 7 ml of THF. 1.36 g (10.6 mmol) of 2-cyclohexylethanol was added to the obtained suspension at 0° C., and they were stirred at 40° C. for 30 minutes. 2.00 g (8.82 mmol) of benzyl 4-chloroacetoacetate was added to the obtained mixture at room temperature, and they were refluxed at 100° C. for 3 hours. 1 N hydrochloric acid was added to the reaction mixture. After the extraction with ethyl acetate, the organic layer was washed with 10% aqueous sodium hydroxide solution and saturated aqueous sodium chloride solution, dried over anhydrous magnesium sulfate and concentrated under reduced pressure. The residue was purified by the silica gel chromatography (hexane/ethyl acetate=4/1) to obtain the title compound. they were refluxed at 100° C. for 3 hours After the extraction with ethyl acetate the organic layer was washed with 10% aqueous sodium hydroxide solution and saturated aqueous sodium chloride solution dried over anhydrous magnesium sulfate concentrated under reduced pressure The residue was purified by the silica gel chromatography (hexane/ethyl acetate=4/1)

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

Procedure: 2-Cyclohexylethanol 15-1 (3.2 g, 25 mmol) and ethyl 4-hydroxybenzoate 15-2 (4.15 g, 25 mmol) were reacted as in Example 14. The product 15-3 was obtained as a waxy solid.

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

Procedure: Dimethyl sulfoxide (DMSO) (3.3 ml, 58.5 mmol) was added dropwise at -78° C. to a solution of oxazolyl dichloride (3.6 ml, 46.8 mmol) in methylene chloride and the mixture was stirred for 15 minutes. To the resulting mixture, a solution of 2-cyclohexylethanol (5.5 ml, 39.0 mmol) in methylene chloride was added dropwise and the mixture was stirred at -78° C. for 1 hour. The reaction was stopped by adding triethylamine (20 ml) and water (100 ml). The reaction mixture was extracted 3 times with diethyl ether. The organic layer was washed 3 times each with saturated aqueous solutions of ammonium chloride and NaCl and dried over anhydrous sodium sulfate. After the solvent was distilled off, the obtained oil was applied to a silica gel column (2.5×40 cm) and eluted with a mixed solution (chloroform:methanol=10:1). The desired fractions were collected and the solvents were distilled off to yield cyclohexylacetaldehyde (2.88 g, 58.4%) as an oil. The same procedure as in Example 2-(2) was performed with ethyl isobutyrate (2.14 ml, 17.8 mmol) and the obtained cyclohexylacetaldehyde (2.25 g, 17.8 mmol) to yield a crystal of 4-cyclohexylmethyl-3,3-dimethyl-2-azetidinone (0.46 g, 13.3%). the mixture was stirred at -78° C. for 1 hour The reaction mixture was extracted 3 times with diethyl ether The organic layer was washed 3 times each with saturated aqueous solutions of ammonium chloride and NaCl dried over anhydrous sodium sulfate After the solvent was distilled off eluted with a mixed solution (chloroform:methanol=10:1) The desired fractions were collected the solvents were distilled off

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

Procedure: 2-Chloro-4-anilinopyrimidine (Reference Example A-9, 700 mg, 3.4 mmol) was dissolved in DCM (70 ml), triphenyl phosphine (1.07 g, 4.1 mmol) and 2-cyclohexyl ethanol (0.57 ml, 4.1 mmol) were added followed by dropwise addition of DEAD (0.646 ml, 4.1 mmol). After 1 hour additional triphenyl phosphine (0.5 g, 2 mmol), 2-cyclohexyl ethanol (0.28 ml, 2 mmol) and DEAD (0.320 ml, 2 mmol) were added and the reaction mixture was stirred overnight at ambient temperature. The solvent was evaporated off and the residue was purified by flash chromatography using EtOAc/petroleum ether (15/85, then 20/80) as the eluent. The solvent was evaporated to give the title product as a colourless oil (368 mg, 37%). NMR (400 MHz, 353K): 0.90 (m, 2H), 1.20 (m, 3H), 1.30 (m, 1H), 1.65 (m, 7H), 3.90 (t, 2H), 4.05 (m, 1H), 6.10 (d, 1H), 7.34 (d, 2H), 7.43 (t, 1H), 7.54 (t, 2H), 7.95 (d, 1H); m/z (ES+) 316 and 318 (MH+). The solvent was evaporated off the residue was purified by flash chromatography The solvent was evaporated