methyl 1-hydroxynaphthalene-2-carboxylate

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

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: To 3.26 g caesium carbonate and 1.01 g methyl 1-hydroxy-2-naphthoate in 10 ml abs. DMF was added 1.21 g 1-bromomethyl-4-trifluoromethyl-benzene and the mixture was reacted for 3 h at room temperature. The reaction was partitioned between water and ethyl acetate and the aqueous layer was extracted with ethyl acetate twice. The combined organic phases were dried over magnesium sulphate and concentrated in vacuo. The resulting residue was purified by chromatography (silica, heptane) to yield 1.62 g of 1-(4-trifluoromethyl-benzyloxy)-naphthalene-2-carboxylic acid methyl ester. the mixture was reacted for 3 h at room temperature The reaction was partitioned between water and ethyl acetate the aqueous layer was extracted with ethyl acetate twice The combined organic phases were dried over magnesium sulphate concentrated in vacuo The resulting residue was purified by chromatography (silica, heptane)

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

Procedure: A solution of 2.3 g (11.4 mmol) of methyl 1-hydroxy-naphthalene-2-carboxylate in 15 ml of dry tetrahydrofuran was treated with 0.51 g (17 mmol) of sodium hydride (80%) and subsequently 2.13 g of 2-methoxyethoxymethyl chloride were added dropwise while cooling with ice. After 3 hours at room temperature the solution was extracted with aqueous sodium hydrogen carbonate solution and the organic phase was separated, dried over sodium sulphate and evaporated under reduced pressure. For purification, the crude product was chromatographed on silica gel using a 9:1 mixture of methylene chloride and ether as the eluent. In addition to 1.55 g of starting material there were obtained 1.2 g of methyl 1-(2-methoxy-ethoxymethyl)-naphthalene-2-carboxylate; MS: 290 (M)+. were added dropwise while cooling with ice After 3 hours at room temperature the solution was extracted with aqueous sodium hydrogen carbonate solution the organic phase was separated dried over sodium sulphate evaporated under reduced pressure For purification the crude product was chromatographed on silica gel using a 9:1 mixture of methylene chloride and ether as the eluent In addition to 1.55 g of starting material there

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

Procedure: A solution of 2.3 g (11.4 mmol) of methyl 1-hydroxy-naphthalene-2-carboxylate in 15 ml of dry tetrahydrofuran was treated with 0.51 g (17 mmol) of sodium hydride (80%) and subsequently 2.13 g of 2-methoxyethoxymethyl chloride were added dropwise while cooling with ice. After 3 hours at room temperature the solution was extracted with aqueous sodium hydrogen carbonate solution and the organic phase was separated, dried over sodium sulphate and evaporated under reduced pressure. For purification, the crude product was chromatographed on silica gel using a 9:1 mixture of methylene chloride and ether as the eluent. In addition to 1.55 g of starting material there were obtained 1.2 g of methyl 1-(2-methoxy-ethoxymethyl)-naphthalene-2-carboxylate; MS: 290 (M)+. were added dropwise while cooling with ice After 3 hours at room temperature the solution was extracted with aqueous sodium hydrogen carbonate solution the organic phase was separated dried over sodium sulphate evaporated under reduced pressure For purification the crude product was chromatographed on silica gel using a 9:1 mixture of methylene chloride and ether as the eluent In addition to 1.55 g of starting material there

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

Procedure: By alkylating methyl 1-hydroxy-naphthalene-2-carboxylate analogously to Example 1 (g) with 2-bromoethyl methyl ether there was obtained methyl 1-(2-methoxy-ethoxy)-naphthalene-2-carboxylate, which was subsequently converted analogously to Example 5 (b)-(c) firstly into [1-(2-methoxy-ethoxy)-naphthalen-2-yl]-methanol and then into 2-chloromethyl-1-(2-methoxy-ethoxy)-naphthalene, which was finally obtained as a beige solid; MS: 250 (M)+.

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

Procedure: By alkylating methyl 1-hydroxy-naphthalene-2-carboxylate analogously to Example 1 (g) with 2-bromoethyl methyl ether there was obtained methyl 1-(2-methoxy-ethoxy)-naphthalene-2-carboxylate, which was subsequently converted analogously to Example 5 (b)-(c) firstly into [1-(2-methoxy-ethoxy)-naphthalen-2-yl]-methanol and then into 2-chloromethyl-1-(2-methoxy-ethoxy)-naphthalene, which was finally obtained as a beige solid; MS: 250 (M)+.

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

Procedure: A mixture of methyl 1-hydroxy-2-naphthoate (500 mg, 2.473 mmol), (R)-pent-4-en-2-ol (0.382 mL, 3.71 mmol), triphenylphosphine (1297 mg, 4.95 mmol) and (Z)-diethyl diazene-1,2-dicarboxylate (0.836 mL, 4.95 mmol) in THF (20 mL) was stirred at rt for 3 h. It was then concentrated and the residue was purified by biotage, eluting with 10% EtOAc/hexane to isolate (S)-methyl 1-(pent-4-en-2-yloxy)-2-naphthoate (500 mg, 74.8%) as an oil. 1H NMR (400 MHz, CDCl3) δ 8.41-8.27 (m, 1H), 7.96-7.81 (m, 2H), 7.69-7.45 (m, 3H), 5.89 (ddt, J=17.2, 10.1, 7.1 Hz, 1H), 5.22-5.04 (m, 2H), 4.49-4.29 (m, 1H), 3.99 (s, 3H), 2.66-2.57 (m, 1H), 2.55-2.46 (m, 1H), 1.28 (d, J=6.4 Hz, 3H). It was then concentrated the residue was purified by biotage eluting with 10% EtOAc/hexane

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

Procedure: A mixture of methyl 1-hydroxy-2-naphthoate (500 mg, 2.473 mmol), (R)-pent-4-en-2-ol (0.382 mL, 3.71 mmol), triphenylphosphine (1297 mg, 4.95 mmol) and (Z)-diethyl diazene-1,2-dicarboxylate (0.836 mL, 4.95 mmol) in THF (20 mL) was stirred at rt for 3 h. It was then concentrated and the residue was purified by biotage, eluting with 10% EtOAc/hexane to isolate (S)-methyl 1-(pent-4-en-2-yloxy)-2-naphthoate (500 mg, 74.8%) as an oil. 1H NMR (400 MHz, CDCl3) δ 8.41-8.27 (m, 1H), 7.96-7.81 (m, 2H), 7.69-7.45 (m, 3H), 5.89 (ddt, J=17.2, 10.1, 7.1 Hz, 1H), 5.22-5.04 (m, 2H), 4.49-4.29 (m, 1H), 3.99 (s, 3H), 2.66-2.57 (m, 1H), 2.55-2.46 (m, 1H), 1.28 (d, J=6.4 Hz, 3H). It was then concentrated the residue was purified by biotage eluting with 10% EtOAc/hexane

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

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