(R)-tert-Butyl 1-(3-methoxybenzyl)pyrrolidin-3-ylcarbamate synthesis

Yield:-

Reaction Conditions:

Stage #1: 3-N-tert-butoxycarbonyl-3-(R)-aminopyrrolidine;3-methoxy-benzaldehydewith sodium tris(acetoxy)borohydride in dichloromethane at 20; for 2 h;
Stage #2: with water;sodium hydrogencarbonate in dichloromethane; for 0.333333 h;

Steps:

450

Preparation 450; To a mixture of tert-butyl (3R)-3-pyrrolidinylcarbamate (450mg) and3-methoxybenzaldehyde (352uL) in CH₂Cl2 (4.5mL) was added sodiumtriacetoxyborohydride (922mg), which was stirred at roomtemperature for 2 hours. To the resultant was added sat. NaHCO₃ aq.,Which was stirred for 20 min. The mixture was extracted with CH₂C1₂.The organic phase was washed with brine and dried over Na₂SO4,filtered, and evaporated in vacuo. The residue was purified bycolumn chromatography on silica gel to give tert-butyl [(3R)-l-(3-methoxybenzyl)-3-pyrrolidinyl]carbamate (744mg) as a off-whitesolid.^XH NMR (200 Mz, CDC1₃) d 1.43 (9H, s), 1.49-1.72 (1H, m), 2.16-2.46(2H, m), 2.58-2.72 (2H, m), 2.80-2.98 (1H, m), 3.63 (2H, br. s),3.82 (3H, s), 4.08-4.31 (1H, br), 4.90-5.14 (1H, br), 6.76-6.95 (3H,m), 7.24 (1H, t, J ? 8.1 Hz);MS (ES+) m/z 307 (M+l).

References:

WO2006/16680,2006,A1 Location in patent:Page/Page column 184