ethyl 5-methylhex-2-ynoate

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

Conditions: temp:160.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

Procedure: To a solution of (S)-5-(4-bicyclo[3.3.1]non-9-yl-phenoxymethyl)-4,5-dihydro-oxazol-2-ylamine (0.600 g, 1.91 mmol) in ethanol (5 mL) was added 0.294 g (2.86 mmol) of 5-methyl-hex-2-ynoic acid ethyl ester. The reaction mixture was heated in a microwave oven at 160° C. for 20 minutes. The reaction mixture was concentrated and purified by chromatography on silica gel eluting with MeOH/CH2Cl2 to afford 0.283 g of the title compound. [α]D25 −11.17 (c 0.537, CHCl3). The reaction mixture was concentrated purified by chromatography on silica gel eluting with MeOH/CH2Cl2

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

Procedure: The title compound was prepared from 4-methyl-pent-1-yne and ethyl chloroformate in accordance with the procedures of G. Cai et al., Tetrahedron, 2006, (5697-5708).

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

Procedure: The title compound was prepared from (S)-5-(4-cyclohexyl-phenoxymethyl)-4,5-dihydro-oxazol-2-ylamine and 5-methyl-hex-2-ynoic acid ethyl ester (prepared from 4-methyl-pent-1-yne and ethyl chloroformate in accordance with the procedures of G. Cai et al., Tetrahedron, 2006, 5697-5708) employing the procedure described in Example 99. [α]D25 −13.93 (c 0.546, CHCl3)

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

Procedure: The title compound was prepared from 4-methyl-pent-1-yne and ethyl chloroformate in accordance with the procedures of G. Cai et al., Tetrahedron, 2006, (5697-5708).

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

Procedure: 5-Methyl-hex-2-ynoic acid ethyl ester 7 (20.97 g) in THF (540 mL), pyridine (60 mL), and 5% Pd/BaSO4 (1.10 g) was hydrogenated in 3.25 hours. The solvent was evaporated, and the light oil was chromatographed on a silica gel coulmn. After recovering some unreacted acetylene, the olefin was eluted with 5% ether in pet ether to give pure fractions of (Z)-5-methyl-hex-2-enoic acid ethyl ester 8 (12.0 g). The solvent was evaporated the light oil was chromatographed on a silica gel coulmn After recovering some unreacted acetylene the olefin was eluted with 5% ether in pet ether

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

Procedure: 5-Methyl-hex-2-ynoic acid ethyl ester 7 (20.97 g) in THF (540 mL), pyridine (60 mL), and 5% Pd/BaSO4 (1.10 g) was hydrogenated in 3.25 hours. The solvent was evaporated, and the light oil was chromatographed on a silica gel coulmn. After recovering some unreacted acetylene, the olefin was eluted with 5% ether in pet ether to give pure fractions of (Z)-5-methyl-hex-2-enoic acid ethyl ester 8 (12.0 g). The solvent was evaporated the light oil was chromatographed on a silica gel coulmn After recovering some unreacted acetylene the olefin was eluted with 5% ether in pet ether

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

Procedure: 1,1-Dibromo-4-methyl-pent-1-ene 6 (40 g, 165.9 mmol) was dissolved in dry THF (120 mL) and cooled to −78° C. While stirring, n-butyllithium (1.6 M solution in hexane, 190.8 mL, 305 mmol) was added dropwise in a few minutes. After 1 hour, ethyl chloroformate (15 mL, 154.5 mmol) was added, and the reaction was stirred overnight during which it warmed to room temperature. It was poured onto water and extracted with ether (3×250 mL), dried on magnesium sulfate and evaporated. The light oil was flash chromatographed on a silica gel column, and the compound was eluted with 10% ether in pet ether to afford 5-methyl-hex-2-ynoic acid ethyl ester 7 (23.6 g, 92%). the reaction was stirred overnight during which it warmed to room temperature It was poured onto water extracted with ether (3×250 mL) dried on magnesium sulfate evaporated chromatographed on a silica gel column the compound was eluted with 10% ether in pet ether

Conditions: temp:160.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

Procedure: To a solution of (S)-5-(4-bicyclo[3.3.1]non-9-yl-phenoxymethyl)-4,5-dihydro-oxazol-2-ylamine (0.600 g, 1.91 mmol) in ethanol (5 mL) was added 0.294 g (2.86 mmol) of 5-methyl-hex-2-ynoic acid ethyl ester. The reaction mixture was heated in a microwave oven at 160° C. for 20 minutes. The reaction mixture was concentrated and purified by chromatography on silica gel eluting with MeOH/CH2Cl2 to afford 0.283 g of the title compound. [α]D25 −11.17 (c 0.537, CHCl3). The reaction mixture was concentrated purified by chromatography on silica gel eluting with MeOH/CH2Cl2

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

Procedure: The title compound was prepared from 4-methyl-pent-1-yne and ethyl chloroformate in accordance with the procedures of G. Cai et al., Tetrahedron, 2006, (5697-5708).

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

Procedure: The title compound was prepared from (S)-5-(4-cyclohexyl-phenoxymethyl)-4,5-dihydro-oxazol-2-ylamine and 5-methyl-hex-2-ynoic acid ethyl ester (prepared from 4-methyl-pent-1-yne and ethyl chloroformate in accordance with the procedures of G. Cai et al., Tetrahedron, 2006, 5697-5708) employing the procedure described in Example 99. [α]D25 −13.93 (c 0.546, CHCl3)

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

Procedure: The title compound was prepared from 4-methyl-pent-1-yne and ethyl chloroformate in accordance with the procedures of G. Cai et al., Tetrahedron, 2006, (5697-5708).