methyl 2-(1,2,3,4-tetrahydroisoquinolin-1-yl)acetate

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 a solution of material from Step 1 (6.71 g, 32.0 mmol) in 175 mL of dichloroethane was added 37% aqueous formaldehyde (22.6 mL, 300 mmol). After about 10 minute, sodium triacetoxyborohydride (31.2 g, 147.0 mmol) was added in 2 to 3 g portions with some cooling to maintain ambient temperature. The mixture was stirred for about 16 hours and DCM and water was added. The mixture was adjusted to pH 9–10 with 5N sodium hydroxide. The organic layer was separated, washed with brine, and then dried (Na2SO4) and concentrated in vacuo. Chromatography (silica gel, 5%(2N ammonia in methanol)/DCM) of the residue afforded about 6.9 g (96%) of the title compound. EIS-MS: 220 (M+1). The organic layer was separated washed with brine dried (Na2SO4) concentrated in vacuo

Conditions: temp:0.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

Procedure: 2-(1,2,3,4-Tetrahydroisoquinolin-1-yl)acetic acid methyl ester (7.49 g, 36.5 mmol) was dissolved in DCM (200 ml), and triethylamine (11.7 ml, 83 mmol) was added thereto. The reaction solution was cooled to 0° C., and a solution of 3,4-dichlorobenzenesulfonyl chloride (8.14 g, 33.2 mmol) in DCM (100 ml) was added dropwise. After 3 h, 0.5 M HCl (100 ml) was added. After phase separation, the organic phase was washed with water, dried (sodium sulfate) and concentrated. Purification was carried out by column chromatography on silica gel (heptane/ethyl acetate 4:1). After phase separation the organic phase was washed with water dried (sodium sulfate) concentrated Purification

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

Procedure: 2-(1,2,3,4-Tetrahydroisoquinolin-1-yl)acetic acid (7.90 g, 41.3 mmol) was dissolved in methanol (200 ml), and H2SO4 (4.4 ml, 82.6 mmol) was added under a nitrogen atmosphere. The reaction solution was heated under reflux and, when the reaction was complete, was stirred overnight at room temperature. The methanol was removed in vacuo and the resulting residue was taken up in ethyl acetate (200 ml). The solution was washed with saturated NaHCO3 solution (150 ml), dried (sodium sulfate) and concentrated. The reaction solution was heated under reflux The methanol was removed in vacuo The solution was washed with saturated NaHCO3 solution (150 ml) dried (sodium sulfate) concentrated

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

Procedure: To a solution of material from Step 1 (6.71 g, 32.0 mmol) in 175 mL of dichloroethane was added 37% aqueous formaldehyde (22.6 mL, 300 mmol). After about 10 minute, sodium triacetoxyborohydride (31.2 g, 147.0 mmol) was added in 2 to 3 g portions with some cooling to maintain ambient temperature. The mixture was stirred for about 16 hours and DCM and water was added. The mixture was adjusted to pH 9-10 with 5N sodium hydroxide. The organic layer was separated, washed with brine, and then dried (Na2SO4) and concentrated in vacuo. Chromatography (silica gel, 5% (2N ammonia in methanol)/DCM) of the residue afforded about 6.9 g (96%) of the title compound. EIS-MS: 220 (M+1). The organic layer was separated washed with brine dried (Na2SO4) concentrated in vacuo

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

Procedure: To Boc-tetrahydoisoquinoline-1-acetic acid (100.4 g, 520.0 mmol), in MeOH (200 mL), was added 400 mL of 2.3 M HCl in methanol. The mixture was stirred overnight and then concentrated to dryness. The resulting residue was dissolved in EtOAc, washed with saturated sodium bicarbonate, brine, dried (Na2SO4), and concentrated to dryness; affording 109.5 g (100%) of the ester. concentrated to dryness The resulting residue was dissolved in EtOAc washed with saturated sodium bicarbonate, brine dried (Na2SO4) concentrated to dryness

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

Procedure: To a solution of material from Step 1 (6.71 g, 32.0 mmol) in 175 mL of dichloroethane was added 37% aqueous formaldehyde (22.6 mL, 300 mmol). After about 10 minute, sodium triacetoxyborohydride (31.2 g, 147.0 mmol) was added in 2 to 3 g portions with some cooling to maintain ambient temperature. The mixture was stirred for about 16 hours and DCM and water was added. The mixture was adjusted to pH 9–10 with 5N sodium hydroxide. The organic layer was separated, washed with brine, and then dried (Na2SO4) and concentrated in vacuo. Chromatography (silica gel, 5% (2N ammonia in methanol)/DCM) of the residue afforded about 6.9 g (96%) of the title compound. EIS-MS: 220 (M+1). The organic layer was separated washed with brine dried (Na2SO4) concentrated in vacuo

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

Procedure: To Boc-tetrahydoisoquinoline-1-acetic acid (100.4 g, 520.0 mmol) in MeOH (200 mL) is added 400 mL of 2.3 M HCl in methanol. The mixture is stirred overnight and then concentrated to dryness. The resulting residue is dissolved in EtOAc and washed with saturated sodium bicarbonate and brine, which is then dried (Na2SO4) and concentrated to dryness to afford about 109.5 g (100%) of the ester. EIS-MS 206 [M+1] concentrated to dryness The resulting residue is dissolved in EtOAc washed with saturated sodium bicarbonate and brine, which is then dried (Na2SO4) concentrated to dryness

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

Procedure: To a solution of material from Step 1 (6.71 g, 32.0 mmol) in 175 mL of dichloroethane was added 37% aqueous formaldehyde (22.6 mL, 300 mmol). After about 10 minute, sodium triacetoxyborohydride (31.2 g, 147.0 mmol) was added in 2 to 3 g portions with some cooling to maintain ambient temperature. The mixture was stirred for about 16 hours and DCM and water was added. The mixture was adjusted to pH 9–10 with 5N sodium hydroxide. The organic layer was separated, washed with brine, and then dried (Na2SO4) and concentrated in vacuo. Chromatography (silica gel, 5%(2N ammonia in methanol)/DCM) of the residue afforded about 6.9 g (96%) of the title compound. EIS-MS: 220 (M+1). The organic layer was separated washed with brine dried (Na2SO4) concentrated in vacuo