Ming Chen (graduate student) and m Roush (famous organic chemist) tly first tota
ID: 514043 • Letter: M
Question
Ming Chen (graduate student) and m Roush (famous organic chemist) tly first total synthesis of Triandomycin C an interesting compound that has anti-HIV properties published the R.Total formation of Lett. 2012, 14, 426-4281. One of the early steps in the synthesis is the ester 13 by addition of the alcohol 11 to the acid chloride 12 (see below). The procedure that Chen and Roush report for synthesizing 13 is shown below (slightly modified). Please use this procedure to answer the following questions. To receive full credit for correct answers, be sure to show your work in conventional dimensional analysis format (also called factor-label method). (2R BR-1-tert-butyldiphenylsilylexy 2-methylhex-5-en-3-yl methacrylate (13. A solution of alcohol 11 (84 g, 5 mmol) and Et N (1.74 mln 12.5 mmol) in CH Clz (50 mL was cooled to 0 C in an ice bath and methacryloyl chloride (078 g. 7,5 mmo) was added slowly. The resulting reaction mixture was allowed to warm to ambient temperature and kept for 12 h. The reaction mixture was diluted with saturated ag. NaHCOo 20 ml.) and brine (20 ml) The organic layer was separated and the aqueous layer was extractod with Euro Gx 25 mL). The combined organic extracts were dried anhydrous magnesium sulfate, filtered, and concentrated under reduced pressure. Purification of the crude product was performed by flash column chromatography 0:1) which ester 13 (.87 g. yield): 4.5 IA6, CHCla. (400 MHz, CDCI, 87.68-762 m, 4H) 7A3 7.33 (m, 6H), 6.041-6.037 (m, IH) 5.77-5.69 (m, lH), 5.51-5.50 (m, IH), 5.21-5.17 (m, lH), 5.07- 5.02 (m. 21), 355 (dd,J- 10.0, 6.8 Hz, IH, 3.49 (dd, J 903-1897 (m, 3H) 1.04 (s 9H, 0.95 (d, J 7.2 Hz 3H. 34.3, 134.0, 1339, 1299, 128.0, 127.9, 125.3 7.8, 73.8, 65.8, 38,7, 36,7, 272, 195, 18.7 7: IR (neat) 3069, 1, 823, 740, 702 cm HRMS: mz for CnHJOySi 293 l, 2858, 1716, 1470, 1428, 1318, 1296, 1167, IM+Hlt calcd 437.2512, found 437.2518. 1. Suppose you are a professional pharmaceutical chemist, and your supervisor asks you to synthesize 13 by following Roush's procedure by starting with 100 gof11. Complete the table below that would likely be in your laboratory notebook. Please show your work on the back of this page being sure to use dimensional analysis. ELN 101.19 (5 Polats per answer)Explanation / Answer
1. if 100 g of alcohol (mwt 368.58) find the table, for this calculation 11 is fixed 100 g as per mentioned in question, find the table for answers
acid chloride 12 is based on above procedure ,
5 mmol required 7.5 mmol
so 1.5 times.
here for 100 g is 0.2713 moles, so 0.2713*1.5 =0.406 moles
so 0.406*104.53 (molecular weight) =42.43 g.
same as Et3N , 5 mmol required 12.5 mmol , so 12.5/5 = 2.5 eq.
here for 100g
=0.2713*2.5=0.678 .
=0.678*101.19
=68.60 g
for conversion of grams to mls
68.60/0.726
=94.49 ml.
same as solvent 5 mmol required 50 ml, 50/5 = 10 times
so 0.2713*10=2.713 lit
for mls conversion 2.713*1000 =2713 ml
2. alcohol 11 2.84 g instead of 1.84 g
so based on 2.84 g of alcohol 11 ,
theoretical yield = ?
as based on chemistry 13 synthesis,combine two molecules 11 amd 12 release one hydrochloride molecules(this neutrlaise with Et3N form salt).
so 368.58+104.53=473.11
=473.11-36.5 (HCl)
=436.61 .product molecular wt.
now 2.84/368.58*436.61
=3.364 g is theoretical yield.
now percent of yield=
obtained yield/theoretical yield
so 1.56/3.364*100
=46.37%
percent of yield =46.37.
3. for recryztalisation , select suitable solvent.
to selection of suitable solvent, check the solubility in different solvents.
the solvent should be less soluble at room temperature or 0-5°C temperature, complete or clearly soluble at reflux or boiling temperature. so this principle for recrystalization(other part which solvent taking impurities).
first solubilty will be check with non-polar solvents like hexane, pentane, diethylether, toluene solvents
other slight polar MDC, ethylacetate, IPA.
or else can try mixture of solvents based on solubility.
Reagent molecular wt. density moles amount needed in g or ml 11 alcohol 368.58 --- 0.2713 100 g 12 acid chloride 104.53 ---- 0.406 42.43 g Et3N 101.19 0.726 0.678 94.49 ml CH2Cl2 solvent 84.93 1.33 --- 2713 ml