ethyl 2-formyl-3-methylbutanoate

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

Procedure: To a solution of (S)-5-(4-cyclohexyl-phenoxymethyl)-4,5-dihydro-oxazol-2-ylamine (0.48 g, 1.74 mmol) (prepared in accordance with the procedures described in Steps 1 and 2 of Example 1 and starting from R-epichlorohydrin and 4-cyclohexylphenol) in ethanol (16 mL) was added 2-formyl-3-methyl-butyric acid ethyl ester (0.33 g, 2.1 mmol). The reaction mixture was heated at reflux for 24 hours. It was then concentrated to remove solvent and loaded on silica gel column. Chromatography with (1-5%) 2-propanol/methylene chloride gave 0.144 g of the title compound. [α]D25 −15.80 (c 0.5, CHCl3). The reaction mixture was heated at reflux for 24 hours It was then concentrated to remove solvent

Conditions: temp:-78.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

Procedure: A solution of diisopropylamine (2.53 g, 25 mmol) in THF (25 mL) was treated with n-butyllithium (1.6M in hexane, 16 mL, 25.6 mmol) at room temperature under N2. The resulting pale yellow solution was cooled to −78° C. A solution of 3-methyl-butyric acid ethyl ester (2.91 g, 22.31 mmol) in THF (7 mL) was added. Stirring was continued for a half hour at −78° C., after which ethyl formate (5.5 g, 75 mmol) was added. The reaction mixture was allowed to warm to room temperature and stirred for three hours under N2. The reaction mixture was quenched with acetic acid (4.5 ml), diluted with diethyl ether, washed with water, brine, and dried (Na2SO4). Silica gel chromatography (methyl acetate/hexane) provided 3.2 g of the title compound as a mixture of isomers. was continued for a half hour at −78° C. to warm to room temperature stirred for three hours under N2 The reaction mixture was quenched with acetic acid (4.5 ml) diluted with diethyl ether washed with water, brine dried (Na2SO4)

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

Procedure: To a solution of (S)-5-(4-cyclohexyl-phenoxymethyl)-4,5-dihydro-oxazol-2-ylamine (0.48 g, 1.74 mmol) (prepared in accordance with the procedures described in Steps 1 and 2 of Example 1 and starting from R-epichlorohydrin and 4-cyclohexylphenol) in ethanol (16 mL) was added 2-formyl-3-methyl-butyric acid ethyl ester (0.33 g, 2.1 mmol). The reaction mixture was heated at reflux for 24 hours. It was then concentrated to remove solvent and loaded on silica gel column. Chromatography with (1-5%) 2-propanol/methylene chloride gave 0.144 g of the title compound. [α]D25 −15.80 (c 0.5, CHCl3). The reaction mixture was heated at reflux for 24 hours It was then concentrated to remove solvent

Conditions: temp:-78.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

Procedure: A solution of diisopropylamine (2.53 g, 25 mmol) in THF (25 mL) was treated with n-butyllithium (1.6M in hexane, 16 mL, 25.6 mmol) at room temperature under N2. The resulting pale yellow solution was cooled to −78° C. A solution of 3-methyl-butyric acid ethyl ester (2.91 g, 22.31 mmol) in THF (7 mL) was added. Stirring was continued for a half hour at −78° C., after which ethyl formate (5.5 g, 75 mmol) was added. The reaction mixture was allowed to warm to room temperature and stirred for three hours under N2. The reaction mixture was quenched with acetic acid (4.5 ml), diluted with diethyl ether, washed with water, brine, and dried (Na2SO4). Silica gel chromatography (methyl acetate/hexane) provided 3.2 g of the title compound as a mixture of isomers. was continued for a half hour at −78° C. to warm to room temperature stirred for three hours under N2 The reaction mixture was quenched with acetic acid (4.5 ml) diluted with diethyl ether washed with water, brine dried (Na2SO4)

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

Procedure: To a solution of (S)-5-(4-cyclohexyl-phenoxymethyl)-4,5-dihydro-oxazol-2-ylamine (0.48 g, 1.74 mmol) (prepared in accordance with the procedures described in Steps 1 and 2 of Example 1 and starting from R-epichlorohydrin and 4-cyclohexylphenol) in ethanol (16 mL) was added 2-formyl-3-methyl-butyric acid ethyl ester (0.33 g, 2.1 mmol). The reaction mixture was heated at reflux for 24 hours. It was then concentrated to remove solvent and loaded on silica gel column. Chromatography with (1-5%) 2-propanol/methylene chloride gave 0.144 g of the title compound. [α]D25 −15.80 (c 0.5, CHCl3). The reaction mixture was heated at reflux for 24 hours It was then concentrated to remove solvent

Conditions: temp:-78.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

Procedure: A solution of diisopropylamine (2.53 g, 25 mmol) in THF (25 mL) was treated with n-butyllithium (1.6M in hexane, 16 mL, 25.6 mmol) at room temperature under N2. The resulting pale yellow solution was cooled to −78° C. A solution of 3-methyl-butyric acid ethyl ester (2.91 g, 22.31 mmol) in THF (7 mL) was added. Stirring was continued for a half hour at −78° C., after which ethyl formate (5.5 g, 75 mmol) was added. The reaction mixture was allowed to warm to room temperature and stirred for three hours under N2. The reaction mixture was quenched with acetic acid (4.5 ml), diluted with diethyl ether, washed with water, brine, and dried (Na2SO4). Silica gel chromatography (methyl acetate/hexane) provided 3.2 g of the title compound as a mixture of isomers. was continued for a half hour at −78° C. to warm to room temperature stirred for three hours under N2 The reaction mixture was quenched with acetic acid (4.5 ml) diluted with diethyl ether washed with water, brine dried (Na2SO4)