Benzyl chloroformate → 2-(1,1-Dimethylethyl) 1-(phenylmethyl) (2S)-1,2-pyrrolidinedicarboxylate

An ice-cooled (0° C.) stirred solution of (S)-proline tert-butyl ester (2) (24.5 g, 143 mmol) and anhydrous diisopropylethylamine (DIPEA) (32.4 mL, 186 mmol) in dry THF (400 mL) was treated with benzylchloroformate (24.6 mL, 172 mmol). After 5 min, the cooling bath and removed and the reaction mixture was stirred at room temperature for 6 h. The mixture was poured into ether (500 mL) and 1 N HCl (400 mL). The organic fraction was washed with H2O (200 mL) and brine (200 mL), and dried over MgSO4. The solvent was removed in vacuo and the resultant oil (43.0 g; 99% was used without further purification. A portion (1 g) was purified by flash chromatography (SiO2; 10% EtOAc in hexane, Rƒ0.25) yielding a clear colorless oil (990 mg): 1H NMR (200 MHz, CDCl3) δ 7.22-7.42 (m, 5H, Ar—H), 5.02-5.22 (m, 2H, OCH2), 4.18-4.20 (m, 1H, α-CH), 3.40-3.65 (m, 2H, δ-CH2), 2.10-2.24 (m, 1H), 1.80-2.10 (m, 3H), 1.35 & 1.43 (s, 9H, C(CH3)3).

1. customthe cooling bath and removed
2. additionThe mixture was poured into ether (500 mL) and 1 N HCl (400 mL)
3. washThe organic fraction was washed with H2O (200 mL) and brine (200 mL)
4. dry with materialdried over MgSO4
5. customThe solvent was removed in vacuo
6. custom99% was used without further purification
7. customA portion (1 g) was purified by flash chromatography (SiO2; 10% EtOAc in hexane, Rƒ0.25)

ORD record

ord-584fb735153544f5b189f6790b134d19

Source dataset

uspto-grants-2003_10

DOI

10.6084/m9.figshare.5104873.v1

Patent number

US06638941B1