N-(4-oxo-1-adamantyl)acetamide

反応条件: temp:0.00; pressure:0.00; stir:; See reaction.notes.procedure_details.

実験手順: Solid NaHCO3 (1.2 mol) and mCPBA (1 2 mmol, 77% purity) were added to a solution of ketone 1A (0.6 mmol) in DCM (5 mL) at 0° C. The reaction mixture was allowed to warm to rt and was maintained for 1 h. The reaction mixture was diluted with a saturated, aqueous solution of sodium bisulfate (10 mL) and was extracted with DCM (3×10 mL). The combined organic layers were dried (Na2SO4) and concentrated. The residue was purified by silica gel chromatography (10/90 to 30/70 EtOAc/hexane) to provide lactone 16A in 90% yield. Data: LC/MS (ESR) m/z 224 [M+1]+. was maintained for 1 h was extracted with DCM (3×10 mL) The combined organic layers were dried (Na2SO4) concentrated The residue was purified by silica gel chromatography (10/90 to 30/70 EtOAc/hexane)

反応条件: temp:0.00; pressure:0.00; stir:; See reaction.notes.procedure_details.

実験手順: Solid NaHCO3 (1.2 mol) and mCPBA (1 2 mmol, 77% purity) were added to a solution of ketone 1A (0.6 mmol) in DCM (5 mL) at 0° C. The reaction mixture was allowed to warm to rt and was maintained for 1 h. The reaction mixture was diluted with a saturated, aqueous solution of sodium bisulfate (10 mL) and was extracted with DCM (3×10 mL). The combined organic layers were dried (Na2SO4) and concentrated. The residue was purified by silica gel chromatography (10/90 to 30/70 EtOAc/hexane) to provide lactone 16A in 90% yield. Data: LC/MS (ESR) m/z 224 [M+1]+. was maintained for 1 h was extracted with DCM (3×10 mL) The combined organic layers were dried (Na2SO4) concentrated The residue was purified by silica gel chromatography (10/90 to 30/70 EtOAc/hexane)

反応条件: temp:0.00; pressure:0.00; stir:; See reaction.notes.procedure_details.

実験手順: A solution of diazomethane (Diazald, 2.70 g) in MeOH (15 mL) was added dropwise to a mixture of ketone 1A (997 mg) and KOH (3.81 g) in MeOH (10 mL) and water (1.8 mL) at 0° C. over a period of 1.5 h. The reaction mixture was allowed to warm to rt and was maintained for 16 h. The resulting suspension was concentrated and was diluted with water (50 mL). The resulting aqueous suspension was extracted with ether (1×), then with DCM (2×), and the combined organic layers were dried (Na2SO4) and concentrated. The residue was purified by silica gel chromatography (0/100 to 10/90 MeOH/EtOAc) to provide 964 mg of ketone 8A as a white solid. Data: LC/MS (ESR) m/z 222 [M+1]+, 244 [M+Na]+. was maintained for 16 h The resulting suspension was concentrated was diluted with water (50 mL) The resulting aqueous suspension was extracted with ether (1×) with DCM (2×), and the combined organic layers were dried (Na2SO4) concentrated The residue was purified by silica gel chromatography (0/100 to 10/90 MeOH/EtOAc)

反応条件: temp:0.00; pressure:0.00; stir:; See reaction.notes.procedure_details.

実験手順: A solution of N-(4-oxoadamantan-1-yl)acetamide (1A) (20 mmol) in 200 mL of concentrated, aqueous HCl was heated in a sealed pressure tube at 130° C. for 20 h. The solvent was removed under reduced pressure to give amine 1B as an HCl salt in 90% yield as an off-white solid. Data: LC/MS (ESR) m/z 166 [M+1]+. The solvent was removed under reduced pressure

反応条件: temp:0.00; pressure:0.00; stir:; See reaction.notes.procedure_details.

実験手順: A solution of N-(4-oxoadamantan-1-yl)acetamide (1A) (20 mmol) in 200 mL of concentrated, aqueous HCl was heated in a sealed pressure tube at 130° C. for 20 h. The solvent was removed under reduced pressure to give amine 1B as an HCl salt in 90% yield as an off-white solid. Data: LC/MS (ESR) m/z 166 [M+1]+. The solvent was removed under reduced pressure

反応条件: temp:0.00; pressure:0.00; stir:; See reaction.notes.procedure_details.

実験手順: A stirred solution of 1-acetamido-4-oxoadamantane (420 mg, 2.0 mmol) in MeOH (20 mL) was cooled in an ice bath and an NaBH4 caplet (1.0 g, 26 mmol) was added. The mixture was stirred over the weekend at rt and evaporated to dryness. The residue was taken up in EtOAc (90 mL), washed with 5% aq HCl (20 mL) and satd aq NaHCO3 (20 mL), and dried over MgSO4. Removal of the solvent left 1-acetamido-4-hydroxyadamantane (170 mg, 40%). evaporated to dryness washed with 5% aq HCl (20 mL) dried over MgSO4 Removal of the solvent left 1-acetamido-4-hydroxyadamantane (170 mg, 40%)

反応条件: temp:0.00; pressure:0.00; stir:; See reaction.notes.procedure_details.

実験手順: Mixture of 10 mmole 1-acetylaminoadamantane (Aldrich chemical Company, Inc.), 1 mmole of N-hydroxyphthalimide (NHPI), 0.05 mmole of vanadium(III)acetylacetonato (V(AA)3) and 25 mL of acetic acid was stirred under an oxygen atmosphere and the conditions represented in Table 1 (temperature and time). The products in the reaction mixture were analyzed by gas chromatography, and, as a result, 1-acetylamino-3-adamantanol (compound 1), 1-acetylamino-3,5-adamatanediol (compound 2) and 1-acetylamino-4-adamantanone (compound 3) were obtained with conversions and yields represented in Table 1.

反応条件: temp:0.00; pressure:0.00; stir:; See reaction.notes.procedure_details.

実験手順: A stirred solution of 1-acetamido-4-oxoadamantane (420 mg, 2.0 mmol) in MeOH (20 mL) was cooled in an ice bath and an NaBH4 caplet (1.0 g, 26 mmol) was added. The mixture was stirred over the weekend at rt and evaporated to dryness. The residue was taken up in EtOAc (90 mL), washed with 5% aq HCl (20 mL) and satd aq NaHCO3 (20 mL), and dried over MgSO4. Removal of the solvent left 1-acetamido-4-hydroxyadamantane (170 mg, 40%). evaporated to dryness washed with 5% aq HCl (20 mL) dried over MgSO4 Removal of the solvent left 1-acetamido-4-hydroxyadamantane (170 mg, 40%)

反応条件: temp:0.00; pressure:0.00; stir:; See reaction.notes.procedure_details.

実験手順: A solution of 1.2 g of nitryltetrafluoroborate in 15 ml of acetonitrile is cooled to 0° C. and a solution of 2.17 g of 5-bromo-2-oxoadamantane [preparation is described in H. W. Geluk, SYNTHESIS, p. 374 (1972)] in 15 ml of acetonitrile is added with rapid stirring and cooling. The reaction mixture is stirred for 30 minutes then poured into water and extracted with diethyl ether. The diethyl ether extract is washed with 5% sodium bicarbonate solution and water and dried over magnesium sulfate. The solvent is removed under reduced pressure to give N-(2-oxoadamantan-5-yl)acetamide. Substitution of an equivalent quantity of N-(2-oxoadamantan-5-yl)acetamide for the methyl 2-oxoadamantane-1-carbamate of Example 57 and substantial repetition of the procedures detailed therein provides methyl L-tyrosyl-D-methionylglycyl-L-phenylalanyl-5-amino-2-adamantanecarboxylate hydrochloride which is represented by the formula ##STR68## cooling The reaction mixture is stirred for 30 minutes extracted with diethyl ether The diethyl ether extract is washed with 5% sodium bicarbonate solution and water dried over magnesium sulfate The solvent is removed under reduced pressure

反応条件: temp:0.00; pressure:0.00; stir:; See reaction.notes.procedure_details.

実験手順: Mixture of 10 mmole 1-acetylaminoadamantane (Aldrich chemical Company, Inc.), 1 mmole of N-hydroxyphthalimide (NHPI), 0.05 mmole of vanadium (III) acetylacetonato (V(AA)3) and 25 mL of acetic acid was stirred under an oxygen atmosphere and the conditions represented in Table 1 (temperature and time). The products in the reaction mixture were analyzed by gas chromatography, and, as a result, 1-acetylamino-3-adamantanol (compound 1), 1-acetylamino-3,5-adamantanediol (compound 2) and 1-acetylamino-4-adamantanone (compound 3) were obtained with conversions and yields represented in Table 1.