1-bromo-1-methylcyclohexane

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

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

Conditions: temp:100.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

Procedure: A mixture of 1-bromo-1-methylcyclohexane (7.200 g, 3.0 equiv), tributyltin hydride (8 mL, 2.2 equiv), methyl 2-(benzyloxycarbonylamino)acrylate (3.120 g, 13.26 mmol, 1.0 equiv), and 2,2′-azobisisobutyronitrile (0.370 g, 0.17 equiv) in benzene (30 mL) was heated at 100° C. for 6 h. After the reaction mixture was evaporated under reduced pressure, the crude methyl 2-(benzyloxycarbonylamino)-3-(1-methylcyclohexyl)propanoate was used directly in the next step without further purification. MS ESI +ve m/z 356 (M+Na). After the reaction mixture was evaporated under reduced pressure the crude methyl 2-(benzyloxycarbonylamino)-3-(1-methylcyclohexyl)propanoate was used directly in the next step without further purification

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

Procedure: To a suspension of freshly ground magnesium turnings (0.40 g, 16 mmol) in 100 mL of ether was added about 20 percent of a 100 ml ether solution containing 2.5 g (14 mmol) of bromo-methyl-cyclohexane. The reaction was heated to reflux and the remaining bromo-methyl-cyclohexane solution added over one hour. After 1 hour, an additional 150 mg of freshly ground Mg was added and after 5 hours, the mixture was cooled to room temperature. The Grignard solution was added over one hour to a mixture of 2.45 g (13 mmol) of 2-bromo-indene, 100 mg of NiCl2(dppp) (0.15 mmol) and 100 mL of ether. The system was gently heated to reflux overnight and then cooled and quenched by adding 150 mL of 1.0 M aqueous hydrochloric acid. The product was isolated and purified (hexanes/silica) as for 2-benzyl-indene. The reaction was heated to reflux an additional 150 mg of freshly ground Mg was added and after 5 hours The system was gently heated to reflux overnight cooled quenched by adding 150 mL of 1.0 M aqueous hydrochloric acid The product was isolated purified (hexanes/silica) as for 2-benzyl-indene

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

Procedure: To a suspension of freshly ground magnesium turnings (0.40 g, 16 mmol) in 100 mL of ether was added about 20 percent of a 100 ml ether solution containing 2.5 g (14 mmol) of bromo-methyl-cyclohexane. The reaction was heated to reflux and the remaining bromo-methyl-cyclohexane solution added over one hour. After 1 hour, an additional 150 mg of freshly ground Mg was added and after 5 hours, the mixture was cooled to room temperature. The Grignard solution was added over one hour to a mixture of 2.45 g (13 mmol) of 2-bromo-indene, 100 mg of NiCl2(dppp) (0.15 mmol) and 100 mL of ether. The system was gently heated to reflux overnight and then cooled and quenched by adding 150 mL of 1.0 M aqueous hydrochloric acid. The product was isolated and purified (hexanes/silica) as for 2-benzyl-indene. The reaction was heated to reflux an additional 150 mg of freshly ground Mg was added and after 5 hours The system was gently heated to reflux overnight cooled quenched by adding 150 mL of 1.0 M aqueous hydrochloric acid The product was isolated purified (hexanes/silica) as for 2-benzyl-indene

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: Ethyl (Z)-2-(hydroxyimino)-3-oxobutyrate (5.86 g, 36.8 mmol), 1-bromo-1-methylcyclohexane (6.01 g 36.8 mmol), and silver trifluoromethanesulphonate (9.45 g, 36.8 mmol) were reacted together by a similar method to that described in Example 9a to give the title compound (4.45 g, 50%); νmax (film) 2970, 1745, 1690, 1590, 1370, 1320, 1230, 1070, and 990 cm-1 ; δH (60 MHz, CDCl3), 1.31 (3H, t, J 7 Hz), 1.48 (3H, s), 1.1-2.2 (8H, m), 2.35 (3H, s), and 4.30 (2H, q, J 7 Hz).

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

Procedure: Ethyl (Z)-2-hydroxyimino-3-oxobutyrate (3.18 g, 20 mmol) and 1-bromo-1-methylcyclohexane (3.54 g, 20 mmol) in dry dioxane (15 ml) were stirred together in the dark and silver trifluoromethanesulphonate (5.13 g, 20 mmol) was added portionwise over 4 h. After a total of 100 h the mixture was filtered through Kieselguhr and the residue was washed well with dioxane. The filtrate was evaporated in vacuo, toluene was added and evaporated in vacuo and the residual oil was dissolved in ethyl acetate and washed with dilute aqueous NaHCO3, followed by water and brine. Ater drying (MgS4) the ethyl acetate was evaporated in vacuo and the residual oil was chromatographed on silica gel, to give the title compound as a yellow oil (3.49 g; 69%); νmax (CH2Cl2) 2945, 1740, 1685, 1370, 1320, 1235, 1070 and 1005 cm-1 ; δH (60 MHz, CDCl3) 1.35 (6H, s superimposed on t), 1.4-2.0 (10H, m), 2.37 (3H, s), 4.55 (2H, q, J 7 Hz). was added portionwise over 4 h After a total of 100 h the mixture was filtered through Kieselguhr the residue was washed well with dioxane The filtrate was evaporated in vacuo, toluene was added evaporated in vacuo the residual oil was dissolved in ethyl acetate washed with dilute aqueous NaHCO3 Ater drying (MgS4) the ethyl acetate was evaporated in vacuo the residual oil was chromatographed on silica gel

Conditions: temp:100.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

Procedure: A mixture of 1-bromo-1-methylcyclohexane (7.200 g, 3.0 equiv), tributyltin hydride (8 mL, 2.2 equiv), methyl 2-(benzyloxycarbonylamino)acrylate (3.120 g, 13.26 mmol, 1.0 equiv), and 2,2′-azobisisobutyronitrile (0.370 g, 0.17 equiv) in benzene (30 mL) was heated at 100° C. for 6 h. After the reaction mixture was evaporated under reduced pressure, the crude methyl 2-(benzyloxycarbonylamino)-3-(1-methylcyclohexyl)propanoate was used directly in the next step without further purification. MS ESI +ve m/z 356 (M+Na). After the reaction mixture was evaporated under reduced pressure the crude methyl 2-(benzyloxycarbonylamino)-3-(1-methylcyclohexyl)propanoate was used directly in the next step without further purification

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

Procedure: To a suspension of freshly ground magnesium turnings (0.40 g, 16 mmol) in 100 mL of ether was added about 20 percent of a 100 ml ether solution containing 2.5 g (14 mmol) of bromo-methyl-cyclohexane. The reaction was heated to reflux and the remaining bromo-methyl-cyclohexane solution added over one hour. After 1 hour, an additional 150 mg of freshly ground Mg was added and after 5 hours, the mixture was cooled to room temperature. The Grignard solution was added over one hour to a mixture of 2.45 g (13 mmol) of 2-bromo-indene, 100 mg of NiCl2(dppp) (0.15 mmol) and 100 mL of ether. The system was gently heated to reflux overnight and then cooled and quenched by adding 150 mL of 1.0 M aqueous hydrochloric acid. The product was isolated and purified (hexanes/silica) as for 2-benzyl-indene. The reaction was heated to reflux an additional 150 mg of freshly ground Mg was added and after 5 hours The system was gently heated to reflux overnight cooled quenched by adding 150 mL of 1.0 M aqueous hydrochloric acid The product was isolated purified (hexanes/silica) as for 2-benzyl-indene