methyl 3-(hydroxymethyl)benzoate

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: A solution of methyl 3-(hydroxymethyl)benzoate (845 mg, 5.09 mmol) in methanol (15 mL) was treated with 1 M NaOH (aq) (15.300 mL, 15.30 mmol), and the reaction was stirred overnight at room temperature. The methanol was removed under reduced pressure, and the remaining aqueous solution was washed 3× with 10 mL of diethyl ether. The aqueous phase was acidified to pH 1 with concentrated HCl, then extracted 3× with 20 mL of ethyl acetate. The combined organic phases were washed with brine, dried over sodium sulfate, and concentrated in-vacuo to yield the title compound (680 mg, 4.47 mmol, 88% yield) as a colorless powder. MS (ESI+)=153.10, (M+H)+. The methanol was removed under reduced pressure the remaining aqueous solution was washed 3× with 10 mL of diethyl ether extracted 3× with 20 mL of ethyl acetate The combined organic phases were washed with brine dried over sodium sulfate concentrated in-vacuo

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

Procedure: A solution of 3-(methoxycarbonyl)benzoic acid (1.05 g, 5.83 mmol) in THF (25 mL) was cooled to 0° C., and treated with the dropwise addition of 2.0 M borane-methylsulfide complex in THF (14.57 mL, 29.1 mmol) at a rate which did not allow the temperature to exceed 5° C. The mixture was stirred at 0° C. for 15 minutes, then allowed to warm to room temperature and stirred for 4 hours. The reaction was cooled to 0° C. and quenched with the addition of small pieces of ice, causing vigorous gas evolution. When gas evolution had ceased, the mixture was diluted with brine and extracted 3× with ethyl acetate. The combined organic phases were washed 3× with dilute bleach to remove residual methyl sulfide, 3× with saturated sodium carbonate to remove any unreacted acid, 1× with water, and 1× with brine, then dried over sodium sulfate and concentrated in vacuo to yield the title compound (845 mg, 5.09 mmol, 87% yield) as a colorless oil. to exceed 5° C to warm to room temperature stirred for 4 hours The reaction was cooled to 0° C. quenched with the addition of small pieces of ice the mixture was diluted with brine extracted 3× with ethyl acetate The combined organic phases were washed 3× with dilute bleach to remove residual methyl sulfide, 3× with saturated sodium carbonate to remove any unreacted acid, 1× with water, and 1× with brine dried over sodium sulfate concentrated in vacuo

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

Procedure: A mixture of 4.75 g (28.6 mmols) of m-methoxycarbonylbenzyl alcohol and 3.6 g (28.6 mmols) of N,N'-diisopropylcarbodiimide was stirred with 50 mg (0.51 mmols) of cuprous chloride at room temperature for 24 hours. The reaction was then diluted with 10 ml of hexane and eluted through a short column of neutral alumina with 20% ethyl acetate-hexane to give 8.0 g (96%) of N,N'-diisopropyl-O-(m-methoxycarbonylbenzyl)-isourea as a colorless oil. eluted through a short column of neutral alumina with 20% ethyl acetate-hexane

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

Procedure: 4.00 g of methyl 3-(hydroxymethyl)benzoate was dissolved in 80 mL of methylene chloride, to which 9.47 g of triphenylphosphine was added in small portions in an ice bath followed by addition of 12.00 g of carbon tetrabromide in small portions, and this solution was stirred for one hour at room temperature. The reaction mixture was concentrated under reduced pressure, and the resultant residue was purified by silica gel column chromatography [eluent; hexane:ethyl acetate=2:1] to yield 5.02 g of methyl 3-(bromomethyl)benzoate as colorless oil. was added in small portions in an ice bath The reaction mixture was concentrated under reduced pressure the resultant residue was purified by silica gel column chromatography [eluent; hexane:ethyl acetate=2:1]

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

Procedure: A solution of methyl 3-(hydroxymethyl)benzoate (845 mg, 5.09 mmol) in methanol (15 mL) was treated with 1 M NaOH (aq) (15.300 mL, 15.30 mmol), and the reaction was stirred for about 16 hours at room temperature. At the conclusion of this period, the methanol was removed under reduced pressure, and the remaining aqueous solution was washed 3× with 10 mL of diethyl ether. The aqueous phase was acidified to pH 1 with concentrated HCl, and then extracted 3× with 20 mL of ethyl acetate. The combined organic phases were washed with brine, dried over sodium sulfate, and concentrated in vacuo to yield 3-(hydroxymethyl)benzoic acid (680 mg, 4.47 mmol, 88% yield) as a colorless powder. MS (ESI+)=153.10, (M+H)+. At the conclusion of this period, the methanol was removed under reduced pressure the remaining aqueous solution was washed 3× with 10 mL of diethyl ether extracted 3× with 20 mL of ethyl acetate The combined organic phases were washed with brine dried over sodium sulfate concentrated in vacuo

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

Procedure: A solution of 3-(methoxycarbonyl)benzoic acid (1.05 g, 5.83 mmol) in THF (25 mL) was cooled to 0° C., and then treated with the dropwise addition of 2.0 M borane-methylsulfide complex in THF (14.57 mL, 29.1 mmol) at a rate which did not allow the temperature to exceed 5° C. The mixture was stirred at 0° C. for 15 minutes, and then allowed to warm to room temperature where it stirred for 4 hours. After this time, the reaction was cooled to 0° C. and then quenched with the addition of small pieces of ice, causing vigorous gas evolution. When gas evolution had ceased, the mixture was diluted with brine and extracted 3× with ethyl acetate. The combined organic phases were washed 3× with diluted bleach to remove residual methyl sulfide, 3× with saturated sodium carbonate to remove any unreacted acid, 1× with water, 1× with brine, dried over sodium sulfate and then concentrated in vacuo to yield the methyl 3-(hydroxymethyl)benzoate (845 mg, 5.09 mmol, 87% yield) as a colorless oil. to exceed 5° C to warm to room temperature where it stirred for 4 hours After this time, the reaction was cooled to 0° C. quenched with the addition of small pieces of ice the mixture was diluted with brine extracted 3× with ethyl acetate The combined organic phases were washed 3× with diluted bleach to remove residual methyl sulfide, 3× with saturated sodium carbonate to remove any unreacted acid, 1× with water, 1× with brine dried over sodium sulfate concentrated in vacuo

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

Procedure: A solution of methyl 3-(hydroxymethyl)benzoate (845 mg, 5.09 mmol) in methanol (15 mL) was treated with 1 M NaOH (aq) (15.300 mL, 15.30 mmol), and the reaction was stirred for about 16 hours at room temperature. At the conclusion of this period, the methanol was removed under reduced pressure, and the remaining aqueous solution was washed 3× with 10 mL of diethyl ether. The aqueous phase was acidified to pH 1 with concentrated HCl, and then extracted 3× with 20 mL of ethyl acetate. The combined organic phases were washed with brine, dried over sodium sulfate, and concentrated in vacuo to yield 3-(hydroxymethyl)benzoic acid (680 mg, 4.47 mmol, 88% yield) as a colorless powder. MS (ESI+)=153.10, (M+H)+. At the conclusion of this period, the methanol was removed under reduced pressure the remaining aqueous solution was washed 3× with 10 mL of diethyl ether extracted 3× with 20 mL of ethyl acetate The combined organic phases were washed with brine dried over sodium sulfate concentrated in vacuo

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

Procedure: A solution of 3-(methoxycarbonyl)benzoic acid (1.05 g, 5.83 mmol) in THF (25 mL) was cooled to 0° C., and then treated with the dropwise addition of 2.0 M borane-methylsulfide complex in THF (14.57 mL, 29.1 mmol) at a rate which did not allow the temperature to exceed 5° C. The mixture was stirred at 0° C. for 15 minutes, and then allowed to warm to room temperature where it stirred for 4 hours. After this time, the reaction was cooled to 0° C. and then quenched with the addition of small pieces of ice, causing vigorous gas evolution. When gas evolution had ceased, the mixture was diluted with brine and extracted 3× with ethyl acetate. The combined organic phases were washed 3× with diluted bleach to remove residual methyl sulfide, 3× with saturated sodium carbonate to remove any unreacted acid, 1× with water, 1× with brine, dried over sodium sulfate and then concentrated in vacuo to yield the methyl 3-(hydroxymethyl)benzoate (845 mg, 5.09 mmol, 87% yield) as a colorless oil. to exceed 5° C to warm to room temperature where it stirred for 4 hours After this time, the reaction was cooled to 0° C. quenched with the addition of small pieces of ice the mixture was diluted with brine extracted 3× with ethyl acetate The combined organic phases were washed 3× with diluted bleach to remove residual methyl sulfide, 3× with saturated sodium carbonate to remove any unreacted acid, 1× with water, 1× with brine dried over sodium sulfate concentrated in vacuo

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

Procedure: A mixture of 4.75 g (28.6 mmols) of m-methoxycarbonylbenzyl alcohol and 3.6 g (28.6 mmols) of N,N'-diisopropylcarbodiimide was stirred with 50 mg (0.51 mmols) of cuprous chloride at room temperature for 24 hours. The reaction was then diluted with 10 ml of hexane and eluted through a short column of neutral alumina with 20% ethyl acetate-hexane to give 8.0 g (96%) of N,N'-diisopropyl-O-(m-methoxycarbonylbenzyl)-isourea as a colorless oil. eluted through a short column of neutral alumina with 20% ethyl acetate-hexane