Tetrahydrofuran → Rac-(cis)-tert-butyl-2-(hydroxymethyl)-3-phenylpyrrolidine-1-carboxylate

To a stirred mixture of rac-(cis)-1-(tert-butoxycarbonyl)-3-phenylpyrrolidine-2-carboxylic acid (0.77 g, 2.6 mmol) (prepared as described by Damour et al. Synlett 1999, 2, 189-192) in THF (10.00 mL, 122 mmol) was added BH3●THF (9.3 mL, 1.0 M in THF, 9.3 mmol) slowly at 0° C. The resulting mixture was stirred at room temperature overnight. The mixture was then cooled to 0° C., and the resulting mixture was quenched with MeOH, concentrated, and the remaining residue was diluted with 1.0 N aqueous NaOH (10 mL), and extracted with EtOAc (10 mL×3). The organic layers were washed with brine, dried over Na2SO4, and concentrated to give a residue which was purified with flash column chromatography (pure hexane →30% EtOAc in hexanes) to obtain the desired product as a colorless sticky syrup, which solidified upon standing. LCMS (API-ES) m/z (%): 278.4 (100%, M+H); 1H NMR (400 MHz, CDCl3) δ ppm (mixture of rotatomers) 1.50 (s, 9H) 2.10-2.17 (m, 2H), 3.33 (d, J=4.70 Hz, 2H), 3.42-3.51 (m, 1H), 3.60-3.67 (m, 2H), 4.26-4.33 (m, 1H) 7.23 (d, J=11.74 Hz, 2H), 7.30-7.39 (m, 3H).

1. temperatureThe mixture was then cooled to 0° C.
2. customthe resulting mixture was quenched with MeOH
3. concentrationconcentrated
4. additionthe remaining residue was diluted with 1.0 N aqueous NaOH (10 mL)
5. extractionextracted with EtOAc (10 mL×3)
6. washThe organic layers were washed with brine
7. dry with materialdried over Na2SO4
8. concentrationconcentrated
9. customto give a residue which
10. customwas purified with flash column chromatography (pure hexane →30% EtOAc in hexanes)

ORD record

ord-4fde6bdf182040f399cbc27852393b40

Source dataset

uspto-grants-2011_04

DOI

10.6084/m9.figshare.5104873.v1

Patent number

US07919504B2