反应详情

Crude N-t-butyloxycarbonyl-(S)-prolinal (2.34 g, 11.7 mmol) was dissolved in dichloromethane (90 ml). A 5.6 M solution of dimethylamine in ethanol (4.19 ml, 23.5 mmol) was added. 0.4 nm Mol sieves (10.0 g) was added. Sodium triacetoxyborohydride 7.47 g, 35.2 mmol) and glacial acetic acid (1.34 ml, 23.5 mmol) were added successively. The reaction mixture was stirred for 3 days. It was filtered through a plug of celite. The celite was washed with methanol (150 ml). An 1N aqueous solution of sodium hydroxide (150 ml) and tert-butyl methyl ether (150 ml) were added. The phases were separated. The aqueous phase was extracted with tert-butyl methyl ether (3×100 ml). The combined organic layers were dried over magnesium sulfate. The solvent was removed in vacuo. The crude product was purified by flash chromatography on silica (90 g), using dichloromethane/methanol/25% aqueous ammonia (100:10:1) as eluent, to give 1.29 g of (2S)-2-((dimethylamino)methyl)pyrrolidine-1-carboxylic acid tert-butyl ester.

1. addition0.4 nm Mol sieves (10.0 g) was added
2. filtrationIt was filtered through a plug of celite
3. washThe celite was washed with methanol (150 ml)
4. additionAn 1N aqueous solution of sodium hydroxide (150 ml) and tert-butyl methyl ether (150 ml) were added
5. customThe phases were separated
6. extractionThe aqueous phase was extracted with tert-butyl methyl ether (3×100 ml)
7. dry with materialThe combined organic layers were dried over magnesium sulfate
8. customThe solvent was removed in vacuo
9. customThe crude product was purified by flash chromatography on silica (90 g)