Thylbutanoate 3 (5.five g, 42 mmol) in 30 mL of DMF, TBDPSCl (0.95 equiv) was added at room temperature. The mixture was stirred for four h, then solvent was removed under decreased pressure. The residue was dissolved in CH2Cl2. The organic layer was washed with H2O (three 30 mL), brine and dried more than Na2SO4. Solvent was removed beneath reduced stress and the crude was purified by chromatography applying 5 EtOAc/hexane as eluent to obtain product 5 as a clear oil (15 g, 99 ). 1H NMR (400 MHz, CDCl3) 7.79 7.30 (m, 10H), three.69 (s, 3H), three.59 (dd, J = 3.3, 12 Hz, 2H), 2.63-2.60 (m, 2H), two.32-2.20 (m, 1H), 1.09 (s, 9H), 1.02 (d, J = six.6 Hz, 3H); 13C NMR (100 MHz, CDCl3) 173.five, 137.eight, 133.8, 129.7, 126.9, 68.7, 51.9, 38.7, 26.eight, 19.7, 16.1. HRMS (ESI, TOF): m/z = 371.0222, calcd for C22H31O3Si [M+H]+ 371.0242.Preparation of (S)-4-(tert-Butyldiphenylsilyloxy)-3-methylbutanal (6)A modification of S1PR2 Antagonist drug reported procedure20 was made use of. Beneath an atmosphere of argon, to an oven dried flask was added [Ir(COD)Cl]2 (ten.1 mg, 0.015 mmol) and 1.five mL of CH2Cl2. Then diethyl silane (529 mg, six.0 mmol) was added along with the resulting mixture was stirred at 23 for 1 minute. Immediately after P/Q-type calcium channel Antagonist Gene ID addition of methyl (S)-4-((tert-butyldiphenylsilyl)oxy)-3methylbutanoate five (3.0 mmol), the mixture was stirred at 23 for 1 h. Then add a different portion of [Ir(COD)Cl]2 (ten.1 mg, 0.015 mmol) and diethyl silane (265 mg, 3.0 mmol) for the mixture and let it to stir 23 for two h. The reaction was diluted with diethyl ether and quenched by 0.1 M HCl. Following stirring for 20 minutes, the layers have been separated and also the aqueous layer was extracted with CH2Cl2. The combined organic layers were dried with MgSO4, and concentrated beneath vacuum. Purification with the residue by flash chromatography on silica gel, eluting with 10 15 CH2Cl2/hexanes gave the preferred aldehyde six as colorless oil (766 mg, 75 ). 1H NMR (400 MHz, CDCl3) 9.86 (t, J = 2.1 Hz, 1H), 7.81 7.74 (m, 4H), 7.54 7.47 (m, 6H), 3.70 (dd, J = 9.9, five.1 Hz, 1H), three.57 (dd, J = 9.9, six.9 Hz, 1H), two.69 (ddd, J = 15.9, 5.7, 2.1 Hz, 1H), two.48 2.39 (m, 1H), 2.35 (ddd, J = 15.9, 7.2, two.1 Hz, 1H), 1.18 (s, 9H), 1.05 (d, J = six.7 Hz, 3H); 13C NMR (100 MHz, CDCl3) 202.five, 135.six, 135.six, 133.6, 133.5 129.8, 127.8, 68.5, 48.2, 31.3, 27.0, 19.three, 16.9. IR (CH2Cl2) n (cm-1) 3070, 2931, 2858, 2360, 1724, 1469, 1427, 1111, 806.three, 740.7, 702.1. HRMS (ESI, TOF): m/z = 347.2021, calcd For C21H28O2SiLi [M+H]+ 347.2019.J Org Chem. Author manuscript; out there in PMC 2014 December 06.Khumsubdee et al.PageTypical Procedure for -Chlorination in the Aldehyde NIH-PA Author Manuscript NIH-PA Author Manuscript NIH-PA Author ManuscriptJ Org Chem. Author manuscript; offered in PMC 2014 December 06.A modification of reported procedure23 was used. 5-Benzyl-2,two,3,-trimethylimidazolidin-4one trifluoroacetic acid salt (13.five mg, 0.05 mmol) in chloroform (1 mL) is cooled to -30 for five minutes prior to addition of two,three,four,5,6,6-hexachloro-2,4-cyclohexadien-1-one (181 mg, 0.6 mmol). The aldehyde 6 (170 mg, 0.5 mmol) was added for the yellow mixture. The resulting mixture was stirred at -30 for eight h. The reaction was then warmed to 0 and MeOH (1 mL) was added for the mixture, followed by NaBH4 (80 mg, two mmol). After stirring at 0 for five minutes, the reaction was quenched by 1 M KHSO4. The aqueous solution was extracted with EtOAc three times. The combined organic layers were dried with MgSO4, and concentrated in vacuo. Purification on the residue by flash chromatography on silica gel, e.