methyl 3-(aminomethyl)-4-hydroxycyclopentane-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:; See reaction.notes.procedure_details.

Procedure: To a stirred suspension of the crude (1SR,3SR,4RS)-3-aminomethyl-4-hydroxy-cyclopentanecarboxylic acid methyl ester (189 mg) at r.t. in DMF (5 ml) under an argon atmosphere were added N-ethyldiisopropylamine (0.74 ml), BOP (531 mg) and 5-chloro-2-thiophenecarboxylic acid (195 mg). The reaction mixture was stirred over night, then diluted with EtOAc and washed with H2O. The aqueous phase was back extracted with EtOAc. The combined organics were washed with H2O and brine, dried (MgSO4), filtered and concentrated. The crude product was purified by column chromatography (silica gel; gradient: CH2Cl2→CH2Cl2/MeOH 93:7) to give (1SR,3SR,4RS)-3-{[(5-chloro-thiophene-2-carbonyl)-amino]-methyl}-4-hydroxy-cyclopentanecarboxylic acid methyl ester (111 mg) as light brown gum. MS: 318.0 ([M+H]+). washed with H2O The aqueous phase was back extracted with EtOAc The combined organics were washed with H2O and brine dried (MgSO4) filtered concentrated The crude product was purified by column chromatography (silica gel; gradient: CH2Cl2→CH2Cl2/MeOH 93:7)

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

Procedure: To a stirred suspension of the crude (1SR,3SR,4RS)-3-aminomethyl-4-hydroxy-cyclopentanecarboxylic acid methyl ester (189 mg) at r.t. in DMF (5 ml) under an argon atmosphere were added N-ethyldiisopropylamine (0.74 ml), BOP (531 mg) and 5-chloro-2-thiophenecarboxylic acid (195 mg). The reaction mixture was stirred over night, then diluted with EtOAc and washed with H2O. The aqueous phase was back extracted with EtOAc. The combined organics were washed with H2O and brine, dried (MgSO4), filtered and concentrated. The crude product was purified by column chromatography (silica gel; gradient: CH2Cl2→CH2Cl2/MeOH 93:7) to give (1SR,3SR,4RS)-3-{[(5-chloro-thiophene-2-carbonyl)-amino]-methyl}-4-hydroxy-cyclopentanecarboxylic acid methyl ester (111 mg) as light brown gum. MS: 318.0 ([M+H]+). washed with H2O The aqueous phase was back extracted with EtOAc The combined organics were washed with H2O and brine dried (MgSO4) filtered concentrated The crude product was purified by column chromatography (silica gel; gradient: CH2Cl2→CH2Cl2/MeOH 93:7)

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

Procedure: To a stirred suspension of the crude (1SR,3SR,4RS)-3-aminomethyl-4-hydroxy-cyclopentanecarboxylic acid methyl ester (189 mg) at r.t. in DMF (5 ml) under an argon atmosphere were added N-ethyldiisopropylamine (0.74 ml), BOP (531 mg) and 5-chloro-2-thiophenecarboxylic acid (195 mg). The reaction mixture was stirred over night, then diluted with EtOAc and washed with H2O. The aqueous phase was back extracted with EtOAc. The combined organics were washed with H2O and brine, dried (MgSO4), filtered and concentrated. The crude product was purified by column chromatography (silica gel; gradient: CH2Cl2→CH2Cl2/MeOH 93:7) to give (1SR,3SR,4RS)-3-{[(5-chloro-thiophene-2-carbonyl)-amino]-methyl}-4-hydroxy-cyclopentanecarboxylic acid methyl ester (111 mg) as light brown gum. MS: 318.0 ([M+H]+). washed with H2O The aqueous phase was back extracted with EtOAc The combined organics were washed with H2O and brine dried (MgSO4) filtered concentrated The crude product was purified by column chromatography (silica gel; gradient: CH2Cl2→CH2Cl2/MeOH 93:7)

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

Procedure: To a stirred solution of (1SR,3SR,4RS)-3-cyano-4-hydroxy-cyclopentanecarboxylic acid methyl ester (185 mg) at r.t. in methanol (5 ml) under an argon atmosphere were added benzyl chloride (0.38 ml) and 10% Pd/C (50 mg). The mixture was stirred at r.t. under a hydrogen atmosphere (balloon) overnight. The catalyst was filtered off and washed with methanol. The filtrate was concentrated to leave a brown viscous oil. This was taken up in 10 ml sat. aq. NaHCO3 and extracted with CH2Cl2/MeOH 9:1 (3×10 ml) and CH2Cl2/MeOH 4:1 (10 ml). A white solid started to precipitate out of the biphasic mixture which was filtered off. The filtrate was neutralized by the addition of 1 N HCl and concentrated to leave crude (1SR,3SR,4RS)-3-aminomethyl-4-hydroxy-cyclopentane-carboxylic acid methyl ester as a light brown solid (189 mg). The catalyst was filtered off washed with methanol The filtrate was concentrated to leave a brown viscous oil extracted with CH2Cl2/MeOH 9:1 (3×10 ml) and CH2Cl2/MeOH 4:1 (10 ml) to precipitate out of the biphasic mixture which was filtered off The filtrate was neutralized by the addition of 1 N HCl concentrated

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

Procedure: To a stirred solution of (1SR,3SR,4RS)-3-cyano-4-hydroxy-cyclopentanecarboxylic acid methyl ester (185 mg) at r.t. in methanol (5 ml) under an argon atmosphere were added benzyl chloride (0.38 ml) and 10% Pd/C (50 mg). The mixture was stirred at r.t. under a hydrogen atmosphere (balloon) overnight. The catalyst was filtered off and washed with methanol. The filtrate was concentrated to leave a brown viscous oil. This was taken up in 10 ml sat. aq. NaHCO3 and extracted with CH2Cl2/MeOH 9:1 (3×10 ml) and CH2Cl2/MeOH 4:1 (10 ml). A white solid started to precipitate out of the biphasic mixture which was filtered off. The filtrate was neutralized by the addition of 1 N HCl and concentrated to leave crude (1SR,3SR,4RS)-3-aminomethyl-4-hydroxy-cyclopentane-carboxylic acid methyl ester as a light brown solid (189 mg). The catalyst was filtered off washed with methanol The filtrate was concentrated to leave a brown viscous oil extracted with CH2Cl2/MeOH 9:1 (3×10 ml) and CH2Cl2/MeOH 4:1 (10 ml) to precipitate out of the biphasic mixture which was filtered off The filtrate was neutralized by the addition of 1 N HCl concentrated