Ral HPLC (Chiralcel OD, Hex/iPrOH 99:1, 1 mL/min, 25 ), tr 16.05 min (key diastereomer), tr 23.68 min (minor diastereomer).NIH-PA Author Manuscript NIH-PA Author ManuscriptJ Org Chem. Author manuscript; out there in PMC 2014 December 06.Khumsubdee et al.Web page(2R,3R)-4-((tert-Butyldiphenylsilyl)oxy)-2-fluoro-3-methylbutan-1-ol (anti-8) The compound was ready as outlined by the standard -fluorination procedure catalysed by (R)-5-benzyl-2,2,three,-trimethylimidazolidin-4-one P2Y12 Receptor Antagonist Purity & Documentation dichloroacetic acid salt. Purification by flash chromatography afforded anti-8 as a colorless oil (153 mg, 85 isolated yield). 1H NMR (400 MHz, CDCl3) 7.74 7.69 (m, 4H), 7.51 7.41 (m, 6H), four.72 (dtd, J = 48.eight, 6.four, 3.1 Hz, 1H), 3.97 3.75 (m, 2H), three.67 three.64 (m, 2H), 2.28 (br, 1H), 2.11 2.00 (m, 1H), 1.12 (s, 9H), 0.99 (dd, J = 7.0, 0.eight Hz, 3H); 13C NMR (one hundred MHz, CDCl3) 135.six (d, J = four.five Hz), 133.3 (d, J = eight.two Hz), 129.8 (s), 127.eight (d, J = 1.six Hz), 95.four (d, J = 171.0 Hz), 65.two (d, J = six.0 Hz), 63.7 (d, J = 22.six Hz), 37.four (d, J = 19.six Hz), 26.9 (s), 11.7 (d, J = 5.8 Hz); 19F NMR (282 MHz, CDCl3) -198.46 -198.93 (m). IR (CH2Cl2) n (cm-1) 3356, 3071, 2932, 2859, 2361, 1470, 1427, 1389, 1362, 1111, 1034. HRMS (ESI, TOF): m/z = 361.2035, calcd For C21H30FO2Si [M+H]+ 361.1999. The diastereoselectivity was 1.0:58, determined by 19F NMR and confirmed by Chiral HPLC (Chiralcel OD, Hex/iPrOH 99:1, 1 mL/min, 25 ), tr 16.05 min (minor diastereomer), tr 23.68 min (big diastereomer). Relative NK1 Inhibitor Purity & Documentation stereochemistry determination of eight: considering the fact that each catalyst and reaction situation are identical to what has been reported, plus the reaction is catalyst controlled; the stereochemistry was assigned according to MacMillan’s fluorinated solution. The solution can’t be very easily converted to any identified structure.NIH-PA Author Manuscript NIH-PA Author Manuscript NIH-PA Author ManuscriptTypical Procedure for the -Amination in the AldehydeA modification of reported procedure38 was made use of. Dibenzyl azodicarboxylate (90 , 1.29 g, 3.9 mmol) and proline (70 mg, 0.six mmol) in MeCN (10 mL) have been cooled down to -3 . The aldehyde (1.02 g three.0 mmol) was then added along with the mixture was stirred at -3 for two h. The reaction was steadily warmed to 20 inside ca. 1 h. The mixture was then cooled to 0 , treated with MeOH (three mL) and NaBH4 (240 mg, 6.0 mmol) and was stirred for five min at 0 . The reaction was quenched by 1M KHSO4. The aqueous solution was extracted with EtOAc three times. The combined organic layers had been dried with MgSO4, and concentrated in vacuo. Purification with the residue by flash chromatography on silica gel, eluting with 15 EtOAc/hexanes gave the preferred alcohol as white foamy solid.J Org Chem. Author manuscript; accessible in PMC 2014 December 06.Khumsubdee et al.PageNIH-PA Author ManuscriptDibenzyl 1-((2R,3S)-4-((tert-Butyldiphenylsilyl)oxy)-1-hydroxy-3-methylbutan-2yl)hydrazine-1,2-dicarboxylate (anti-9) The compound was prepared as outlined by the common -amination procedure catalysed by (R)-Proline. Purification by flash chromatography afforded anti-9 as a white foamy solid (1.54 g, 80 isolated yield). 1H NMR (400 MHz, CDCl3) 7.70 7.67 (m, 4H), 7.50 7.27 (m, 16H), six.85 (d, J = 31.1 Hz, 1H), 5.37 5.ten (m, 4H), 4.45 4.12 (m, 2H), three.80 three.41 (m, 4H), 1.95 1.66 (m, 1H), 1.12 1.09 (m, 9H), 0.99 0.88 (m, 3H); 13C NMR (one hundred MHz, CDCl3) 159.1, 157.4, 135.six, 133.three, 133.two, 129.6, 129.eight, 128.7, 128.six, 128.two, 127.9, 127.eight, 127.7, 68.62, 65.88, 65.56, 60.37, 35.six, 26.9, 19.three, 15.1. IR (CH2Cl2) n (cm-1) 335.