Acetic Acid → tert-Butyl (2R,4R)-4-hydroxy-2-(hydroxymethyl)pyrrolidine-1-carboxylate

Temperature

0 °C

(2R,4R)-1-(tert-Butyloxycarbonyl)-2-carbomethoxy-4-hydroxypyrrolidine 36 (7.0 g, 28.6 mmol) was dissolved in dry THF (100 ml) and cooled in ice salt bath under argon atmosphere. To this cold solution was added lithium borohydride (1.88 g, 85.8 mmol) in small portions during 15 min period. After the addition of lithium borohydride, the reaction mixture was allowed to stir at 0° C. for 1 h followed by 15 h at room temperature under argon. The solution was cooled to 0° C. and diluted with water (50 ml) and the pH was adjusted with AcOH to 6. The reaction was evaporated to dryness and dissolved in EtOAc (200 ml), washed with water (100 ml) and brine (100 ml). The EtOAc extract was dried and evaporated to dryness. The residue was purified by flash column chromatography over silica gel using CH2Cl2 →EtOAc as the eluent. The pure fractions were collected and evaporated to dryness to afford 5.00 g (81%) of clear oil. The oil on standing gave colorless solid. mp: 95-97C. 1HNMR (CDCl3): 1.45 (s, 9H, Boc), 1.90 (dd, 1H), 2.34 (m, 1H), 3.40 -3.62 (m, 3H), 4.00 (m, 2H), 4.28 (bs, 1H), 4.44 (m, 1H).

1. temperaturecooled in ice salt bath under argon atmosphere
2. waitfollowed by 15 h at room temperature under argon
3. temperatureThe solution was cooled to 0° C.
4. customThe reaction was evaporated to dryness
5. dissolutiondissolved in EtOAc (200 ml)
6. washwashed with water (100 ml) and brine (100 ml)
7. extractionThe EtOAc extract
8. customwas dried
9. customevaporated to dryness
10. customThe residue was purified by flash column chromatography over silica gel
11. customThe pure fractions were collected
12. customevaporated to dryness

ORD record

ord-57b55b604ea549f2888041ddc5ba1542

Source dataset

uspto-grants-1999_10

DOI

10.6084/m9.figshare.5104873.v1

Patent number

US05969135