methyl cyclopentene-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: According to the procedure of Example 53, Step 1, using (R)-N-benzyl-N-α-methylbenzylamine (4.2 mL, 4.24 g, 20 mmol), n-butyllithium (2.4 M, 7.4 mL), methyl 1-cyclopentene-1-carboxylate (1.3 mL, 1.29 g, 10.2 mmol), and iodoethane (1.6 mL, 3.12 g, 20 mmol), methyl (1S,2R)-2-amino-1-ethylcyclopentanecarboxylate was obtained as a mixture of two components (1.103 g) after purification on silica gel, eluting with 2% ethyl acetate/hexanes.

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

Procedure: According to the procedure of Example 53, Step 1, using (R)-N-benzyl-N-α-methylbenzylamine (4.2 mL, 4.24 g, 20 mmol), n-butyllithium (2.4 M, 7.4 mL), methyl 1-cyclopentene-1-carboxylate (1.3 mL, 1.29 g, 10.2 mmol), and iodomethane (1.3 mL). methyl (1S,2R)-2-{benzyl[(l R)-1-phenylethyl]amino}-1-methylcyclopentanecarboxylate (2.804 g, 7.97 mmol, 78%) was obtained as a brown oil after column chromatography on silica gel eluting with 5% ethyl acetate/hexanes. 1H NMR (400 MHz, CHLOROFORM-D) δ ppm 0.63 (s, 3H) 1.18-1.29 (m, 5H) 1.52-1.64 (m, 1H) 1.74-1.83 (m, J=12.44, 7.67, 7.67, 2.53 Hz, 1H) 1.85-1.92 (m, 1H) 2.03-2.12 (m, 3H) 2.88 (dd, J=10.86, 7.33 Hz, 1H) 3.50-3.54 (m, 3H) 3.57-3.64 (m, 1H) 3.72-3.77 (m, 1H) 3.83 (q, J=6.82 Hz, 1H) 7.17-7.21 (m, 1H) 7.24-7.35 (m, 6H) 7.50 (d, J=7.33 Hz, 2H).

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

Procedure: According to the procedure of Example 53, Step 1, using (R)-N-benzyl-N-α-methylbenzylamine (4.2 mL, 4.24 g, 20 mmol), n-butyllithium (2.4 M, 7.4 mL), methyl 1-cyclopentene-1-carboxylate (1.3 mL, 1.29 g, 10.2 mmol), and iodomethane (1.3 mL). methyl (1S,2R)-2-{benzyl[(l R)-1-phenylethyl]amino}-1-methylcyclopentanecarboxylate (2.804 g, 7.97 mmol, 78%) was obtained as a brown oil after column chromatography on silica gel eluting with 5% ethyl acetate/hexanes. 1H NMR (400 MHz, CHLOROFORM-D) δ ppm 0.63 (s, 3H) 1.18-1.29 (m, 5H) 1.52-1.64 (m, 1H) 1.74-1.83 (m, J=12.44, 7.67, 7.67, 2.53 Hz, 1H) 1.85-1.92 (m, 1H) 2.03-2.12 (m, 3H) 2.88 (dd, J=10.86, 7.33 Hz, 1H) 3.50-3.54 (m, 3H) 3.57-3.64 (m, 1H) 3.72-3.77 (m, 1H) 3.83 (q, J=6.82 Hz, 1H) 7.17-7.21 (m, 1H) 7.24-7.35 (m, 6H) 7.50 (d, J=7.33 Hz, 2H).

Conditions: temp:-78.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

Procedure: According to the procedure of Tet. Asymm., 13, 2002, 1555: To a solution of (R)-N-benzyl-N-α-methylbenzylamine (1.37 mL, 2 eq.) in THF (10 mL) at −78° C. was added n-butyllithium (2.4 M, 2.2 mL, 1.6 eq). The reaction was allowed to stir for 30 min at −78° C. and then methyl 1-cyclopentene-1-carboxylate (0.41 mL, 3.25 mmol, 1 eq) was added dropwise. The reaction was stirred for 3 h at −78° C. and then a solution of (1R)-(−)-(10-camphorsulfonyl)oxaziridine (1.49 g, 2 eq) in THF (12 mL) was added dropwise via cannula. The reaction was allowed to stir at room temperature overnight, and was then taken up in ethyl acetate, washed with NaHCO3 (1×), brine (2×), dried over Na2SO4, filtered and concentrated. Purification by silica chromatography eluting with a gradient of 10-15% ethyl acetate/hexanes afforded methyl (1R,2R)-2-{benzyl[(1R)-1-phenylethyl]amino}-1-hydroxycyclopentanecarboxylate as an off white solid (0.77 g, 69%). MS: 354.2 (M+H)+ The reaction was stirred for 3 h at −78° C. to stir at room temperature overnight washed with NaHCO3 (1×), brine (2×) dried over Na2SO4 filtered concentrated Purification by silica chromatography eluting with a gradient of 10-15% ethyl acetate/hexanes

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 catalytic amount of trifluoroacetic acid was added to a solution of 1-cyclopentene-1-carboxylic acid methyl ester (2.52 g, 20.0 mmol) and N-benzyl-N-(methoxymethyl)-N-trimethylsilylmethylamine (5.00 g, 21.1 mmol) in dichloromethane (40 mL) at room temperature, and the mixture was heated with stirring at room temperature for 15.5 hours. The reaction solution was diluted with dichloromethane (100 mL) and washed with a saturated sodium bicarbonate solution (80 mL). The washed aqueous layer was further extracted with dichloromethane (50 mL). The organic layers were combined and dried over anhydrous sodium sulfate. After filtration, the solvent was evaporated under reduced pressure. The resulting residue was purified by silica gel column chromatography (hexane:ethyl acetate=95:5→90:10→80:20) to give 4.28 g (83%) of the title compound as a colorless transparent oil. the mixture was heated washed with a saturated sodium bicarbonate solution (80 mL) The washed aqueous layer was further extracted with dichloromethane (50 mL) dried over anhydrous sodium sulfate After filtration the solvent was evaporated under reduced pressure The resulting residue was purified by silica gel column chromatography (hexane:ethyl acetate=95:5→90:10→80:20)

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

Procedure: Methyl cyclopent-1-ene-1-carboxylate (30.0 g, 237.8 mmol) was dissolved in 20 mL of dichloromethane and 3-chloroperbenzoic acid (64.4 g, 373.3 mmol) was added. The reaction was allowed to stir vigorously for 2 hours. The reaction mixture was diluted with EtOAc and washed with 0.5 N NaOH. The organic layer was dried over sodium sulfate, filtered and concentrated to give 48.0 grams of methyl 6-oxabicyclo[3.1.0]hexane-1-carboxylate. washed with 0.5 N NaOH The organic layer was dried over sodium sulfate filtered concentrated

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

Procedure: According to the procedure of Example 53, Step 1, using (R)-N-benzyl-N-α-methylbenzylamine (4.2 mL, 4.24 g, 20 mmol), n-butyllithium (2.4 M, 7.4 mL), methyl 1-cyclopentene-1-carboxylate (1.3 mL, 1.29 g, 10.2 mmol), and iodoethane (1.6 mL, 3.12 g, 20 mmol), methyl (1S,2R)-2-amino-1-ethylcyclopentanecarboxylate was obtained as a mixture of two components (1.103 g) after purification on silica gel, eluting with 2% ethyl acetate/hexanes.

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

Procedure: According to the procedure of Example 53, Step 1, using (R)-N-benzyl-N-α-methylbenzylamine (4.2 mL, 4.24 g, 20 mmol), n-butyllithium (2.4 M, 7.4 mL), methyl 1-cyclopentene-1-carboxylate (1.3 mL, 1.29 g, 10.2 mmol), and iodomethane (1.3 mL). methyl (1S,2R)-2-{benzyl[(l R)-1-phenylethyl]amino}-1-methylcyclopentanecarboxylate (2.804 g, 7.97 mmol, 78%) was obtained as a brown oil after column chromatography on silica gel eluting with 5% ethyl acetate/hexanes. 1H NMR (400 MHz, CHLOROFORM-D) δ ppm 0.63 (s, 3H) 1.18-1.29 (m, 5H) 1.52-1.64 (m, 1H) 1.74-1.83 (m, J=12.44, 7.67, 7.67, 2.53 Hz, 1H) 1.85-1.92 (m, 1H) 2.03-2.12 (m, 3H) 2.88 (dd, J=10.86, 7.33 Hz, 1H) 3.50-3.54 (m, 3H) 3.57-3.64 (m, 1H) 3.72-3.77 (m, 1H) 3.83 (q, J=6.82 Hz, 1H) 7.17-7.21 (m, 1H) 7.24-7.35 (m, 6H) 7.50 (d, J=7.33 Hz, 2H).