C([O-])(=O)C.[Na+].[CH:6]1([CH:9]=O)[CH2:8][CH2:7]1.C([BH3-])#N.[Na+].Cl.[CH2:16]([O:18][C:19]([C@@H:21]1[CH2:25][CH2:24][CH2:23][C@@H:22]1[NH2:26])=[O:20])[CH3:17].Cl>CO>[CH2:16]([O:18][C:19]([C@@H:21]1[CH2:25][CH2:24][CH2:23][C@@H:22]1[NH:26][CH2:9][CH:6]1[CH2:7][CH2:8]1)=[O:20])[CH3:17]Sodium acetate (0.423 g, 5.16 mmol), powdered 4 Å molecular sieves (0.60 g), cyclopropanecarboxaldehyde (0.193 mL, 2.58 mmol) and sodium cyanoborohydride (0.324 mg, 5.16 mmol) were added sequentially to a solution of (1R,2S)-2-amino-cyclopentanecarboxylic acid ethyl ester hydrochloride (prepared as described in Example 28b, 0.500 g, 2.58 mmol) in methanol (15 mL) at 25° C. The reaction mixture was stirred at 25° C. for 16 h, then was acidified to pH=2 by the addition of 1.0 M aqueous hydrochloric acid solution. After stirring for 5 min at 25° C., the mixture was partitioned between half-saturated aqueous sodium bicarbonate solution (150 mL) and ethyl acetate (3×50 mL). The organic layers were washed with saturated aqueous brine solution (100 mL), dried over sodium sulfate, filtered, and were concentrated in vacuo. The residue was purified by flash column chromatography (Analogix SuperFlash Column; 0-40% ethyl acetate in hexanes) to afford the desired product, (1R,2S)-2-(cyclopropylmethyl-amino)-cyclopentanecarboxylic acid ethyl ester (0.101 g, 0.478 mmol, 18%), as a clear oil. 1H NMR (400 MHz, CDCl3) δ: 0.00-0.07 (m, 2H), 0.38-0.43 (m, 2H), 0.84-0.91 (m, 1H), 1.23 (t, 3H, J=7.2 Hz), 1.48-1.61 (m, 2H), 1.76-1.87 (m, 3H), 1.91-1.98 (m, 1H), 2.29-2.34 (m, 1H), 2.46-2.51 (m, 1H), 2.84-2.90 (m, 1H), 3.20-3.26 (m, 1H), 3.63 (s, 1H), 4.09 (q, 2H, J=7.0 Hz). LC-MS (ESI) calcd for C12H21NO2 211.16, found 212.4 [M+H+].
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