4-甲基戊醛

反应条件: temp:0.00; pressure:0.00; stir:

反应条件: temp:0.00; pressure:0.00; stir:

反应条件: temp:0.00; pressure:0.00; stir:; See reaction.notes.procedure_details.

实验步骤: The product of Example 84 is treated with 4-methylpentanal according to a procedure similar to Stage 95e in order to produce the expected solid. to produce the expected solid

反应条件: temp:0.00; pressure:0.00; stir:; See reaction.notes.procedure_details.

实验步骤: The product of Example 84 is treated with 4-methylpentanal according to a procedure similar to Stage 95e in order to produce the expected solid. to produce the expected solid

反应条件: temp:0.00; pressure:0.00; stir:

反应条件: temp:0.00; pressure:0.00; stir:

反应条件: temp:0.00; pressure:0.00; stir:; See reaction.notes.procedure_details.

实验步骤: The product of Example 100 is treated with 4-methylpentanal according to a procedure similar to Stage 95e in order to produce the expected solid. to produce the expected solid

反应条件: temp:0.00; pressure:0.00; stir:; See reaction.notes.procedure_details.

实验步骤: The product of Example 100 is treated with 4-methylpentanal according to a procedure similar to Stage 95e in order to produce the expected solid. to produce the expected solid

反应条件: temp:0.00; pressure:0.00; stir:; See reaction.notes.procedure_details.

实验步骤: The product of Example 84 is treated with 4-methylpentanal according to a procedure similar to Stage 95e in order to produce the expected solid. to produce the expected solid

反应条件: temp:150.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

实验步骤: A mixture of (±)-methyl{(2S,4R)-2-[4-(trifluoromethyl)phenyl]piperidin-4-yl}acetate (Intermediate 1, 453 mg, 1.5 mmol), 4-methylpentanal (150 mg, 1.5 mmol) and benzotriazole (178.5 mg, 1.5 mmol) were combined in toluene (15 ml) and the reaction was stirred and heated a 150° C. under Dean-Stark conditions for 16 Hrs. The mixture was evaporated in vacuo to provide a pale gum. The mixture was evaporated in vacuo to provide a pale gum

反应条件: temp:70.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

实验步骤: A mixture of (+)-methyl{(2S,4R)-2-[4-(trifluoromethyl)phenyl]piperidin-4-yl}acetate (Intermediate 2, 3.02 g, 10.0 mmol), 4-methylpentanal (2.1 g, 20.9 mmol) and gold (III) bromide (440 mg, 1 mmol) were combined in water (10 ml) in a 20 ml microwave vial. After the mixture was deoxygenated by evacuate/fill N2, 2-methylbut-1-en-3-yne (1.9 ml, 20.4 mmol) was added. The reaction was stirred and heated a 70° C. in the microwave for 30 min. The mixture was diluted with MeOH and loaded onto 5 SCX cartridges (10 g). Each cartridge was washed with MeOH (50 ml) then 2M NH3 in MeOH (2×50 ml). The ammonia-methanol fractions were combined and evaporated. The residue was taken up in EtOAc and washed with brine (×1), then dried (Na2SO4), filtered and evaporated. The residue was combined with the product from a repeat experiment on the same scale and purified by chromatography (silica, 10% Et2O/isohexane) to give the alkyne (9.1 g) a light yellow oil. 1H NMR (500 MHz, CDCl3): δ 0.83 (6H, d, J 6.6), 1.07-1.22 (2H, m), 1.27-1.45 (3H, m), 1.51-1.58 (2H, m), 1.77-1.85 (2H, m), 1.91 (3H, s), 1.93-2.02 (1H, m), 2.19-2.29 (2H, m), 2.40-2.46 (1H, m), 2.94-2.98 (1H, m), 3.18 (1H, t, J 7.6), 3.50 (1H, dd, J 2.7, 11.2), 3.65 (3H, s), 5.19 (1H, m), 5.25 (1H, s), 7.45 (2H, d, J 7.4), 7.56 (2H, d, J 8.2); M/Z (ES+) 420 (MH+). After the mixture was deoxygenated was added Each cartridge was washed with MeOH (50 ml) evaporated washed with brine (×1) dried (Na2SO4) filtered evaporated purified by chromatography (silica, 10% Et2O/isohexane)

反应条件: temp:0.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

实验步骤: [αS-(αR*,γR*,δR*)]δ-Amino-N-butyl-γ-hydroxy-α-(1-methylethyl)cyclohexanehexanamide hydrochloride (II: 152 mg, 0.328 mmol), sodium acetate (27 mg, 0.328 mmol) and 4-methylpentanal (36 mg, 0.36 mmol) were dissolved in MeOH (3.2 mL). Sodium cyanoborohydride (20.6 mg, 0.328 mmol) was added and the reaction cooled to 0° C. Acetic acid (0.57 mL, 10.0 mmol) was added dropwise. After the addition was complete the reaction was allowed to warm to r.t. over 3 h. Additional acetic acid was added (0.3 mL) and the reaction was allowed to continue for 30 min. The reaction was brought to a pH of one by the addition of 1N HCl and continued stirring for one h. Water (10 mL) was added and the reaction was neutralized by the addition of solid NaHCO3. The aqueous phase was extracted with CHCl3 (3×15 mL). The combined organic extracts were dried (MgSO4), filtered and concentrated in vacuo. Silica gel chromatography (97.5:2.5:0.2 to 96:4:0.2 CH2Cl2 :MeOH:NH4OH gradient) of the concentrate afforded the free amine (76 mg, 56%) which was converted to the hydrochloride salt by treating a MeOH (5 mL) solution of the amine with 1N HCl (0.185 mL). The solvent was removed in vacuo and the residue dissolved in water (20 mL) and EtOH (2 mL). Filtration and lyophilization afforded the title compound (84 mg, 56%) as a white solid. After the addition to warm to r.t. over 3 h The aqueous phase was extracted with CHCl3 (3×15 mL) The combined organic extracts were dried (MgSO4) filtered concentrated in vacuo