The general procedure for the synthesis of tert-butyl (3S,4S)-3-hydroxy-4-(hydroxymethyl)pyrrolidine-1-carboxylate from di-tert-butyl dicarbonate and the compound (CAS: 397883-77-1) is as follows:
1. a suspension of (3S,4S)-N-benzyl-3-hydroxy-4-(hydroxymethyl)pyrrolidine (7) (2.7 g, 13.03 mmol) was mixed with Pearlman's catalyst (200 mg, 1.879 mmol), ammonia (0.2 mL, 28%, 13 mmol), and methanol (20 mL) under hydrogen atmosphere (0.026 g, 13.03 mmol) were stirred for 14 hours.
2. Upon completion of the reaction, the mixture was filtered through diatomaceous earth and concentrated under vacuum to obtain a crude product slurry.
3. The crude product was purified by fast chromatography (eluent ratio 1:1 of 1,4-dioxane and concentrated NH4OH) to afford (3S,4S)-3-hydroxy-4-hydroxymethylpyrrolidine (9) (1.34 g, 88% yield).
4. The 1H and 13C NMR data of the product were in agreement with those of the (3R,4R)-enantiomer as reported by Filichev et al.
5. Boc anhydride (4.99 g, 23 mmol) was added to a solution of compound 10 (1.34 g, 11.4 mmol) in methanol (20 mL) and stirred for 1 hour.
6. After completion of the reaction, the solvent was removed in vacuo and the crude residue was purified by chromatography (eluent 10-20% MeOH:CHCl3) to afford compound 10 (2.20 g, 89% yield) as a colorless slurry.
7. The 1H and 13C NMR data of the product were asymmetric with respect to the (3R,4R)-enantiomer reported by Evans et al. and α20D= +15.2 (c = 1, MeOH), which is the same as that reported for the (3R,4R)-enantiomer but with opposite sign.
