Hydrochloric Acid → (3S)-4-{[(1,1-Dimethylethyl)(diphenyl)silyl]oxy}-3-({[(phenylmethyl)oxy]carbonyl}amino)butanoic acid

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In a 250 ml round-bottomed flask (3S)-4-hydroxy-3-({[(phenylmethyl)oxy]carbonyl}amino)butanoic acid D1 (3.75 g), was dissolved in DMF (30 ml). To the resulting solution imidazole (3.02 g, 44.4 mmol), and TBDPSCl (7.61 ml, 29.6 mmol) were added and the resulting solution left under stirring at room temperature for 15 hours. The reaction mixture was transferred into separatory funnel containing water (300 ml). The pH of the medium was lowered to pH=2 by the addition of a 2 M HCl aqueous solution, then extracted with EtOAc (5×50 mls). The collected organic phase was dried (Na2SO4) and volatiles removed under reduced pressure to give a slightly yellow oil. This crude oil was transferred into a 250 ml round bottom flask with THF (50 ml) and MeOH (10 ml) was added. To the resulting mixture a K2CO3 aqueous solution (9 g of K2CO3 dissolved in 10 ml of water) was added and the reaction left under stirring at room temperature for 3 hours. Volatiles were removed under vacuum and the thick oil obtained was diluted in water (200 ml) and EtOAc (200 ml) and charged into a separatory funnel. The phases were separated and to the organic one water (200 ml) was added and the pH of the medium adjusted to pH=2 by the addition of a 2 M HCl aqueous solution. The phases were separated and the aqueous one back extracted with EtOAc (5×50 mls). The collected organic phases were dried (Na2SO4) and solvent removed under reduced pressure to give an oil that was purified by flash chromatography on silica gel (DCM/MeOH from 100/0 to 90/10). Collected fractions gave the title compound D2 (5.2 g) as a colorless oil. MS: (ES/+) m/z: 492 (M+1). C28H33NO5Si requires 491. 1H NMR (400 MHz, DMSO-d6) δ ppm 8.05-8.28 (m, 4 H), 7.72-8.00 (m, 11 H), 5.47-5.59 (m, 2 H), 4.64-4.80 (m, 1 H), 4.17-4.34 (m, 2 H), 3.20-3.31 (m, 1 H), 3.06-3.20 (m, 1 H), 1.41-1.58 (m, 9 H).

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