methyl 4-oxoadamantane-1-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:

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

Procedure: To a solution of 2-(3-chloro-phenyl)-propane-1,2-diamine (3.4 g) and 4-oxo-adamantane-1-carboxylic acid methyl ester (CAS 56674-88-5, 3.85 g) in ethanol (50 mL) was added acetic acid (0.7 mL) and reaction mixture was refluxed for 4 h, after which it was cooled to 0° C. and NaBH4 was added. The reaction mixture was then slowly brought to room temperature and left at stirring for 17 h. The reaction was monitored by TLC. After completion, water (30 mL) was slowly added. The reaction mixture was concentrated at reduced pressure to remove the ethanol. The aqueous layer was extracted with DCM (3×50 mL) and the organic layers were then dried over Na2SO4 and then concentrated to get crude desired 4-[2-amino-2-(3-chloro-phenyl)-propylamino]-adamantane-1-carboxylic acid methyl ester (6 g) as a mixture of E/Z isomers. The compound was used in the next step without further purification. MS (ESI): 377.4 (MH+). was refluxed for 4 h was then slowly brought to room temperature left The reaction mixture was concentrated at reduced pressure to remove the ethanol The aqueous layer was extracted with DCM (3×50 mL) the organic layers were then dried over Na2SO4 concentrated

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

Procedure: 5 g of 4-oxoadamantane-1-carboxylic acid methyl ester are placed in 26 ml of methanol under nitrogen. 86 ml of a 7N solution of ammonia in methanol are added. The reaction medium is stirred for 18 h, 4 g of sodium borohydride are then added at 0° C. and the reaction medium is stirred for a further 3 h. After concentrating to dryness under reduced pressure and adding water and ethyl acetate, the aqueous phase is extracted three times in ethyl acetate. The organic phases are combined, dried over magnesium sulphate and concentrated to dryness. The crude product obtained is chromatographed on silica gel, elution being carried out with a gradient of heptane/acetone/methanol/NH4OH solvent from 1/0/0 to 4/5/1/0.1. 1.5 g of 4-aminoadamantane-1-carboxylic acid methyl ester are obtained in the form of a mixture of cis/trans (1/3) isomers. the reaction medium is stirred for a further 3 h After concentrating to dryness under reduced pressure adding water and ethyl acetate the aqueous phase is extracted three times in ethyl acetate dried over magnesium sulphate concentrated to dryness The crude product obtained is chromatographed on silica gel, elution

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

Procedure: 1.64 g of 4-Oxo-adamantane-1-carboxylic acid methyl ester (10) were dissolved in 4 mL of 2M aq. LiOH/MeOH (1:1) and stirred overnight at room temperature. Additional 5 ml of the MeOH/LiOH mixture were added and stirring was continued until conversion was complete. The reaction mixture was acidified and extracted three times with ethyl acetate. The organic layer was dried over sodium sulphate and evaporated to dryness to give 1.4 g of (11) as a solid. Rt=0.87 min (Method 3). Detected mass: 195.2 (M+H+). stirring extracted three times with ethyl acetate The organic layer was dried over sodium sulphate evaporated to dryness

Conditions: temp:60.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

Procedure: 38 mL of fuming sulfuric acid were placed in a two necked flask and warmed to 60° C. 1.5 g of 5-hydroxy-2-adamantanone, dissolved in formic acid (8.5 ml) were added dropwise over the course of 2 h. Another 9 mL of formic acid were added over a period of 2 h and stirring was continued at 60° C. for 1 h and at room temperature overnight. Under ice cooling, the reaction mixture was poured on 100 mL of dry methanol, stirred at room temperature for 2 h and subsequently poured onto 400 mL of ice. The aqueous layer was extracted with dichloromethane three times, the combined organic layer was dried over sodium sulphate and evaporated to dryness to give 1.64 g of the desired product. Rt=1.75 min (5). Detected mass: 209.2 (M+H+). were added dropwise over the course of 2 h stirred at room temperature for 2 h The aqueous layer was extracted with dichloromethane three times the combined organic layer was dried over sodium sulphate evaporated to dryness

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

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

Procedure: 5 g of 4-oxoadamantane-1-carboxylic acid methyl ester are placed in 26 ml of methanol under nitrogen. 86 ml of a 7N solution of ammonia in methanol are added. The reaction medium is stirred for 18 h, 4 g of sodium borohydride are then added at 0° C. and the reaction medium is stirred for a further 3 h. After concentrating to dryness under reduced pressure and adding water and ethyl acetate, the aqueous phase is extracted three times in ethyl acetate. The organic phases are combined, dried over magnesium sulphate and concentrated to dryness. The crude product obtained is chromatographed on silica gel, elution being carried out with a gradient of heptane/acetone/methanol/NH4OH solvent from 1/0/0 to 4/5/1/0.1. 1.5 g of 4-aminoadamantane-1-carboxylic acid methyl ester are obtained in the form of a mixture of cis/trans (1/3) isomers. the reaction medium is stirred for a further 3 h After concentrating to dryness under reduced pressure adding water and ethyl acetate the aqueous phase is extracted three times in ethyl acetate dried over magnesium sulphate concentrated to dryness The crude product obtained is chromatographed on silica gel, elution

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

Procedure: 1.64 g of 4-Oxo-adamantane-1-carboxylic acid methyl ester (10) were dissolved in 4 mL of 2M aq. LiOH/MeOH (1:1) and stirred overnight at room temperature. Additional 5 ml of the MeOH/LiOH mixture were added and stirring was continued until conversion was complete. The reaction mixture was acidified and extracted three times with ethyl acetate. The organic layer was dried over sodium sulphate and evaporated to dryness to give 1.4 g of (11) as a solid. Rt=0.87 min (Method 3). Detected mass: 195.2 (M+H+). stirring extracted three times with ethyl acetate The organic layer was dried over sodium sulphate evaporated to dryness

Conditions: temp:60.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

Procedure: 38 mL of fuming sulfuric acid were placed in a two necked flask and warmed to 60° C. 1.5 g of 5-hydroxy-2-adamantanone, dissolved in formic acid (8.5 ml) were added dropwise over the course of 2 h. Another 9 mL of formic acid were added over a period of 2 h and stirring was continued at 60° C. for 1 h and at room temperature overnight. Under ice cooling, the reaction mixture was poured on 100 mL of dry methanol, stirred at room temperature for 2 h and subsequently poured onto 400 mL of ice. The aqueous layer was extracted with dichloromethane three times, the combined organic layer was dried over sodium sulphate and evaporated to dryness to give 1.64 g of the desired product. Rt=1.75 min (5). Detected mass: 209.2 (M+H+). were added dropwise over the course of 2 h stirred at room temperature for 2 h The aqueous layer was extracted with dichloromethane three times the combined organic layer was dried over sodium sulphate evaporated to dryness