tert-butyl 5-bromopentanoate

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: A mixture of tert-butyl 5-bromovalerate (1 g, 4.2 mmol) and the silver salt of 2-hydroxy-1,4-naphthoquinone (0.8 g, 3.84 mmol) in benzene (10 mL), was stirred for 24 h at 50° C. The reaction mixture was filtered through celite and the solvent was removed in vacuo. The residue was purified by flash chromatography (5% methanol in chloroform) to give a yellow solid (384 mg, 30%). 1H NMR (CDCl3) 8.12 (d, J=7.7 Hz, 1H), 7.89 (d, J=7.7 Hz, 1H), 7.70 (t, J=6.1 Hz, 1H), 7.59 (t, J=6.4 Hz, 1H), 5.95 (s, 1H), 4.17 (t, J=5.9 Hz, 2H), 2.35 (t, J=7.2 Hz, 2H), 1.90-2.05 (m, 2H), 1.78-1.90 (m, 2H), 1.47 (s, 9H). The reaction mixture was filtered through celite the solvent was removed in vacuo The residue was purified by flash chromatography (5% methanol in chloroform)

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

Procedure: A mixture of tert-butyl 5-bromovalerate (1 g, 4.2 mmol) and the silver salt of 2-hydroxy-1,4-naphthoquinone (0.8 g, 3.84 mmol) in benzene (10 mL), was stirred for 24 h at 50° C. The reaction mixture was filtered through celite and the solvent was removed in vacuo. The residue was purified by flash chromatography (5% methanol in chloroform) to give a yellow solid (384 mg, 30%). 1H NMR (CDCl3) 8.12 (d, J=7.7 Hz, 1H), 7.89 (d, J=7.7 Hz, 1H), 7.70 (t, J=6.1 Hz, 1H), 7.59 (t, J=6.4 Hz, 1H), 5.95 (s, 1H), 4.17 (t, J=5.9 Hz, 2H), 2.35 (t, J=7.2 Hz, 2H), 1.90-2.05 (m, 2H), 1.78-1.90 (m, 2H), 1.47 (s, 9H). The reaction mixture was filtered through celite the solvent was removed in vacuo The residue was purified by flash chromatography (5% methanol in chloroform)

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

Procedure: A mixture of tert-butyl 5-bromovalerate (1 g, 4.2 mmol) and the silver salt of 2-hydroxy-1,4-naphthoquinone (0.8 g, 3.84 mmol) in benzene (10 mL), was stirred for 24 h at 50° C. The reaction mixture was filtered through celite and the solvent was removed in vacuo. The residue was purified by flash chromatography (5% methanol in chloroform) to give a yellow solid (384 mg, 30%). 1H NMR (CDCl3) 8.12 (d, J=7.7 Hz, 1H), 7.89 (d, J=7.7 Hz, 1H), 7.70 (t, J=6.1 Hz, 1H), 7.59 (t, J=6.4 Hz, 1H), 5.95 (s, 1H), 4.17 (t, J=5.9 Hz, 2H), 2.35 (t, J=7.2 Hz, 2H), 1.90-2.05 (m, 2H), 1.78-1.90 (m, 2H), 1.47 (s, 9H). The reaction mixture was filtered through celite the solvent was removed in vacuo The residue was purified by flash chromatography (5% methanol in chloroform)

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

Procedure: A mixture of tert-butyl 5-bromovalerate (1 g, 4.2 mmol) and the silver salt of 2-hydroxy-1,4-naphthoquinone (0.8 g, 3.84 mmol) in benzene (10 mL), was stirred for 24 h at 50° C. The reaction mixture was filtered through celite and the solvent was removed in vacuo. The residue was purified by flash chromatography (5% methanol in chloroform) to give a yellow solid (384 mg, 30%). 1H NMR (CDCl3) 8.12 (d, J=7.7 Hz, 1H), 7.89 (d, J=7.7 Hz, 1H), 7.70 (t, J=6.1 Hz, 1H), 7.59 (t, J=6.4 Hz, 1H), 5.95 (s, 1H), 4.17 (t, J=5.9 Hz, 2H), 2.35 (t, J=7.2 Hz, 2H), 1.90-2.05 (m, 2H), 1.78-1.90 (m, 2H), 1.47 (s, 9H). The reaction mixture was filtered through celite the solvent was removed in vacuo The residue was purified by flash chromatography (5% methanol in chloroform)

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

Procedure: Potassium carbonate (2.54 g) was added to a solution of 5-bromovaleric acid tert-butyl ester (4.3 g) obtained in Reference Example 1 (1) above and 2-chloropyrimidin-5-ol (2 g) in dimethylsulfoxide (8.6 ml) and the mixture was stirred at 40° C. overnight. The reaction mixture was cooled to room temperature, water and ethyl acetate were added and the organic layer was separated, washed with a saturated brine, dried over magnesium sulfate and concentrated in vacuo. The resulting residue was purified by column chromatography (silica gel; hexane:ethyl acetate=49:1→9:1) to give 5-(2-chloropyrimidin-5-yloxy)valeric acid tert-butyl ester (3.82 g). MS (m/z): 287/289 [M+H]+. The reaction mixture was cooled to room temperature the organic layer was separated washed with a saturated brine dried over magnesium sulfate concentrated in vacuo The resulting residue was purified by column chromatography (silica gel; hexane:ethyl acetate=49:1→9:1)

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

Procedure: Trifluoroacetic acid anhydride (7.7 ml) was added dropwise to a solution of 5-bromovaleric acid (5 g) in tetrahydrofuran (25 ml) under nitrogen atmosphere at −40° C. and the solution was stirred at −40° C. for 30 minutes. To the mixture, was added tert-butanol (25 ml) at −40° C. and the stirring was continued for 3 hours while the temperature was gradually raised up to room temperature. Water and ethyl acetate were added to the mixture and the organic layer was separated, washed with a saturated sodium hydrogen carbonate aq. solution three times and then a saturated brine, dried over magnesium sulfate and concentrated in vacuo to give 5-bromovaleric acid tert-butyl ester (5.88 g). MS (m/z): 237/239 [M+H]+. the stirring was continued for 3 hours while the temperature was gradually raised up to room temperature the organic layer was separated washed with a saturated sodium hydrogen carbonate aq. solution three times a saturated brine, dried over magnesium sulfate concentrated in vacuo

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

Procedure: A mixture of tert-butyl 5-bromovalerate (1 g, 4.2 mmol) and the silver salt of 2-hydroxy-1,4-naphthoquinone (0.8 g, 3.84 mmol) in benzene (10 mL), was stirred for 24 h at 50° C. The reaction mixture was filtered through celite and the solvent was removed in vacuo. The residue was purified by flash chromatography (5% methanol in chloroform) to give a yellow solid (384 mg, 30%). 1H NMR (CDCl3) 8.12 (d, J=7.7 Hz, 1H), 7.89 (d, J=7.7 Hz, 1H), 7.70 (t, J=6.1 Hz, 1H), 7.59 (t, J=6.4 Hz, 1H), 5.95 (s, 1H), 4.17 (t, J=5.9 Hz, 2H), 2.35 (t, J=7.2 Hz, 2H), 1.90-2.05 (m, 2H), 1.78-1.90 (m, 2H), 1.47 (s, 9H). The reaction mixture was filtered through celite the solvent was removed in vacuo The residue was purified by flash chromatography (5% methanol in chloroform)

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

Procedure: A mixture of tert-butyl 5-bromovalerate (1 g, 4.2 mmol) and the silver salt of 2-hydroxy-1,4-naphthoquinone (0.8 g, 3.84 mmol) in benzene (10 mL), was stirred for 24 h at 50° C. The reaction mixture was filtered through celite and the solvent was removed in vacuo. The residue was purified by flash chromatography (5% methanol in chloroform) to give a yellow solid (384 mg, 30%). 1H NMR (CDCl3) 8.12 (d, J=7.7 Hz, 1H), 7.89 (d, J=7.7 Hz, 1H), 7.70 (t, J=6.1 Hz, 1H), 7.59 (t, J=6.4 Hz, 1H), 5.95 (s, 1H), 4.17 (t, J=5.9 Hz, 2H), 2.35 (t, J=7.2 Hz, 2H), 1.90-2.05 (m, 2H), 1.78-1.90 (m, 2H), 1.47 (s, 9H). The reaction mixture was filtered through celite the solvent was removed in vacuo The residue was purified by flash chromatography (5% methanol in chloroform)

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

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