With the rapid development and complex challenges of chemical substances, new drug synthesis pathways are usually the most effective.108149-63-9,(R)-tert-Butyl 4-(hydroxymethyl)-2,2-dimethyloxazolidine-3-carboxylate,as a common compound, the synthetic route is as follows.
Dibenzyl diisopropylphosphoramidite (1.067 mL, 3.24 mmol) is added to compound 8540,41 (0.5 g, 2.162 mmol) and 1H-tetrazole (0.454 g, 6.49 mmol) in CH3CN (10 mL) and the mixture stirred for 1 h. The solvent is evaporated and the residue flash chromatographed (EtOAc-hexanes, 1:9 v/v) to give tert-butyl (4R)-4-({[bis(benzyloxy)phosphanyl]oxy}methyl)-2,2-dimethyl-1,3-oxazolidine-3-carboxylate as a colourless oil. This is dissolved in CH2Cl2 (10 mL) cooled in ice-water and MCPBA (m-chloroperoxybenzoic acid) (0.995 g, 4.32 mmol) added and stirred for 30 min. The mixture is diluted with CH2Cl2 (50 mL) and washed with satd aq Na2SO3, satd aq NaHCO3 (3*) then brine, dried and the solvent evaporated. The residue is flash chromatographed (DCM-hexanes-EtOAc, 4:3:1 v/v/v) to give tert-butyl (4R)-4-({[bis(benzyloxy)phosphoryl]oxy}methyl)-2,2-dimethyl-1,3-oxazolidine-3-carboxylate as a colourless oil (0.816 g, 77%). [alpha]22D +21.5 (c 0.57, CHCl3). 1H NMR (500 MHz, CDCl3) 7.34 (s, 10H), 5.08-5.00 (m, 4H), 4.22-4.16 (m, 0.5H), 4.13-4.06 (m, 1H), 3.97-3.83 (m, 3H), 3.77 (q, J = 8.6, 0.5H), 1.52-1.41 (m, 15H). 13C NMR (125.7 MHz) 152.1, 151.4 (C), 135.7 (C), 128.6 (CH), 127.9 (CH), 94.1, 93.6 (C), 80.6, 80.3 (C), 69.4 (CH2), 65.7, 65.3 (CH2), 64.8, 64.6 (CH2), 56.6, 56.5, 56.32, 56.26 (CH), 28.3 (CH3), 27.4, 24.3 (CH3), 26.6, 23.0 (CH3). Referenced to the centre line of CDCl3 at delta 77.0. 31P NMR (202.3 MHz, CDCl3) -1.0 (s), -1.1 (s). ESI-HRMS for C25H34NNaO7P [M+Na]+ calcd 514.1971; found 514.1968. This material (0.77 g, 1.567 mmol) and 10% Pd-C (100 mg) are stirred in EtOH (15 mL) under a hydrogen atmosphere at ambient temperature and pressure for 16 h. The mixture is filtered through cellulose paper and the solvent is evaporated to give {[(4R)-3-[(tert-butoxy)carbonyl]-2,2-dimethyl-1,3-oxazolidin-4-yl]methoxy}phosphonic acid as a colourless gum (480 mg). This is dissolved in 80% aq TFA (10 mL) and left at room temperature for 2 h. The solvent is evaporated and the residue dissolved in H2O (10 mL) and washed with CH2Cl2 (2 * 10 mL) then evaporated. The residue is dissolved in H2O and chromatographed on RP 18 silica gel (H2O) to give 86 as a colourless gum which solidified (0.26 g, 97%). [alpha]22D 0 (c 0.565, H2O). No measurable rotation observed. 1H NMR (500 MHz, D2O) 4.19-4.12 (m, 1H), 4.11-4.03 (m, 1H), 3.90 (dd, J = 12.3, 4.7, 1H), 3.81 (dd, J = 12.3, 6.7, 1H), 3.63 (m, 1H). Referenced to HOD at delta 4.79. 13C NMR (125.7 MHz, D2O) 62.9 (d, J = 3.2, CH2), 59.1 (CH2), 53.5 (d, J = 7.4, CH). Referenced to internal CH3CN at delta delta 1.47. 31P NMR (202.3 MHz, D2O) 0.0 (s). ESI-HRMS for C3H9NO5P [M-H]- calcd 170.0218; found 170.0211.
108149-63-9, As the paragraph descriping shows that 108149-63-9 is playing an increasingly important role.
Reference£º
Article; Clinch, Keith; Crump, Douglas R.; Evans, Gary B.; Hazleton, Keith Z.; Mason, Jennifer M.; Schramm, Vern L.; Tyler, Peter C.; Bioorganic and Medicinal Chemistry; vol. 21; 17; (2013); p. 5629 – 5646;,
Oxazolidine – Wikipedia
Oxazolidine | C3H7NO – PubChem