tert-butyl 2-(cyclopentylamino)acetate

反応条件: temp:0.00; pressure:0.00; stir:

反応条件: temp:0.00; pressure:0.00; stir:

反応条件: temp:0.00; pressure:0.00; stir:

反応条件: temp:0.00; pressure:0.00; stir:

反応条件: temp:0.00; pressure:0.00; stir:

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

実験手順: Sodium cyanoborohydride(1.9 g) was added portionwise to a stirred mixture of cyclopentanone(2.1 g), glycine tert-butyl ester hydrochloride(5.0 g), water(12 ml) and methanol(25 ml) during 15 min at water-bath temperature. The resulting mixture was stirred for 4 hr, diluted with 20% H3PO4 (40 ml) and water(20 ml), and extracted with ether(80 ml). The aqueous layer was made alkaline(pH 10) with 20% NaOH and extracted with CHCl3 (50 ml). The extract was dried(Na2SO4) and concentrated in vacuo to give an oily residue, which was purified by silica gel column chromatography(ethyl acetate:hexane=3:1) to yield N-cyclopentylglycine tert-butyl ester(4.5 g) as a pale yellow oil. extracted with ether(80 ml) extracted with CHCl3 (50 ml) concentrated in vacuo to give an oily residue, which was purified by silica gel column chromatography(ethyl acetate:hexane=3:1)

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

実験手順: To a solution of N-benzyloxycarbonyl-L-valine (50.0 g) and N-cyclopentylglycine t-butyl ester (39.8 g) in dichloromethane (1.3 liter), stirred under nitrogen and cooled in an ice bath to 0°-5° C., was added triethylamine (44.5 g) then bis(2-oxo-3-oxazolidinyl)phosphinic chloride (56.0 g) at 0° C. The stirred mixture was allowed to warm to room temperature overnight before it was evaporated. After the residue was partitioned between water (1 liter) and ethyl acetate (1 liter), the ethyl acetate solution was washed (1N hydrochloric acid (twice), water, saturated sodium bicarbonate, brine), dried (MgSO4) and evaporated. The residue was purified by flash chromatography, eluting with ethyl acetate:dichloromethane (0:100, 5:95, 10:90 and 25:75, successively). A first, mixed fraction was rechromatographed and the product obtained combined with the product obtained from the first chromatography to afford the ester (73.4 g, 85%); TLC, Rf =0.30, ethyl acetate:dichloromethane (5:95); MS, m/e=433 (M+1), 377, 325, 269, 234, 286, 162, 144 91(base). cooled in an ice bath to 0°-5° C. at 0° C was evaporated After the residue was partitioned between water (1 liter) and ethyl acetate (1 liter) the ethyl acetate solution was washed (1N hydrochloric acid (twice), water, saturated sodium bicarbonate, brine), dried (MgSO4) evaporated The residue was purified by flash chromatography eluting with ethyl acetate:dichloromethane (0:100, 5:95, 10:90 and 25:75 A first, mixed fraction was rechromatographed the product obtained obtained from the first chromatography

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

実験手順: 3-Chloroacetylsalicylic acid was combined with N-cyclopentylglycine t-butyl ester and N,N1 -dicyclohexylcarbodiimide at 0° C. in methylene chloride as described in Example I. Similar workup gave crude N-(3-chloroacetylsalicyloyl)-N-cyclopentylglycine t-butyl ester, which was cleaved to N-(3-chloroacetylsalicyloyl)-N-cyclopentylglycine using iodotrimethylsilane prepared in situ as described in Example I. Hydrolysis with aqueous sodium hydroxide (Example IV) provided the title compound.

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

実験手順: N,N1 -Dicyclohexylcarbodiimide (10.3 g, 50 mmol) in methylene chloride (80 ml) was added to 2-acetylthio-3-methoxybenzoic acid (11.3 g, 50 mmol) and N-cyclopentylglycine t-butyl ester (10.0 g, 50 mmol) in methylene chloride (300 ml) at 0°-5° C. Overnight stirring was followed by filtration and washing of the filtrate with dilute hydrochloric acid, sodium bicarbonate solution and brine. Drying and concentration gave a gum which was dissolved in acetonitrile (65 ml), combined with sodium iodide (11.2 g, 75 mmol) and heated to 40°-50° C. Chlorotrimethylsilane (8.1 g, 75 mmol) was introduced and the mixture was heated for 30 minutes, then quenched with water. The organic phase was washed with water, aqueous sodium thiosulfate and brine then concentrated. Aqueous sodium bicarbonate was added to the residue and the resulting solution was washed with methylene chloride and ether, then acidified and extracted with ethyl acetate. The organic portion was dried and concentrated and the residue passed through a silica gel column to provide the amorphous product. was followed by filtration washing of the filtrate with dilute hydrochloric acid, sodium bicarbonate solution and brine Drying concentration gave a gum which heated to 40°-50° C the mixture was heated for 30 minutes quenched with water The organic phase was washed with water, aqueous sodium thiosulfate and brine then concentrated Aqueous sodium bicarbonate was added to the residue the resulting solution was washed with methylene chloride and ether extracted with ethyl acetate The organic portion was dried concentrated to provide the amorphous product

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

実験手順: 2-Acetylthio-3-chlorobenzoic acid (11.5 g, 50 mmol) and N-cyclopentylglycine t-butyl ester (10.0 g, 50 mmol) in methylene chloride (350 ml) were cooled to 0°-5° C., and N,N1 -dicyclohexylcarbodiimide (10.3 g, 50 mmol) in methylene chloride (50 ml) was added. The mixture was stirred overnight. The DCC-urea was filtered and washed with CH2Cl2. The filtrate was then washed 2×125 ml 1 N HCl, 2×125 ml saturated NaHCO3, 2×125 ml brine, dried (MgSO4), filtered and concentrated to give 20.6 g of an oil. The crude product was used without further purification in the next step. The DCC-urea was filtered washed with CH2Cl2 The filtrate was then washed 2×125 ml 1 N HCl, 2×125 ml saturated NaHCO3, 2×125 ml brine dried (MgSO4) filtered concentrated

反応条件: temp:0.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

実験手順: N-Cyclopentylglycine t-butyl ester (8.3 g, 0.042 mole) and 2-acetylthio-3-methylbenzoic acid (8.9 g, 0.042 mole) were combined in 90 ml CH2Cl2. This solution was cooled to 0° C. before adding to it a solution of N,N-dicyclohexylcarbodiimide (8.6 g, 0.042 mole) in 30 ml CH2Cl2 dropwise over 15 minutes. The reaction was allowed to warm slowly to room temperature overnight. to warm slowly to room temperature overnight

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

実験手順: N,N1 -Dicyclohexylcarbodiimide (15.9 g, 77 mmol) in methylene chloride was added slowly to a mixture of 2-acetylthiobenzoic acid (15.2 g, 77 mmol) and N-cyclopentylglycine t-butyl ester (15.4 g) in methylene chloride maintained at 0°-5°. The mixture was brought to room temperature overnight, filtered, and the filtrate washed successively with dilute hydrochloric acid, saturated sodium bicarbonate and saturated sodium chloride solutions. After drying, the organic portion was concentrated, the residue dissolved in ether and the resulting solution filtered. Concentration of the filtrate gave crude N-(2-acetylthiobenzoyl)-N-cyclopentylglycine t-butyl ester as an oil. maintained at 0°-5° filtered the filtrate washed successively with dilute hydrochloric acid, saturated sodium bicarbonate and saturated sodium chloride solutions After drying the organic portion was concentrated the residue dissolved in ether the resulting solution filtered