Trityl-methanol reaction

The use of the differential method of data analysis to determine reaction orders and specific reaction rates is clearly one of the easiest, since it requires only one experiment. However, other effects, such as the presence of a significant reverse reaction, could render the differential method ineffective. In these ca.ses, the method of initial rates could be used to determine the reaction order and the specific rate constant. Here, a series of experiments is carried out at different initial concentrations, C o. and the initial rate of reaction, is determined for each run. The initial rate. Tao h found by differentiating the data and extrapolating to zero time. For example, in the Trityl-Methanol reaction shown in Example 5-1, the initial rate was found to be 0.00028 mol/dm min. By various plotting or numerical analysis techniques relating —to Cao, we can obtain the appropriate rate law. If the rate law is in the form... 

The aziridine-2-carboxaldehyde 56 can also serve as synthon for the synthesis of sphingosines, which are important biomembrane constituents [64]. One possible route involves the addition of an alanate to the aldehyde. In a later stage of this synthetic plan the aziridine can be opened, either via the intermediacy of an oxazoline or directly with dilute acid. Unfortunately, the reaction of aldehyde 56 with a vinylalanate has a poor diastereoselectivity of 3 2. Therefore, an alternative approach was considered, namely one involving the addition of a vinylzinc reagent to the aldehyde thereby employing our N-tritylaziridinediphenyl-methanol 51 as the chiral catalyst. Gratifyingly, only one diastereomer was obtained. Reductive removal of the trityl function, acetylation of the hydroxy... 

Furthermore, several functionalities remained unaffected, namely the acid-labile TBDMS or PMB groups.118 Deprotection yields were in the range of 85-95% when methanol was used at room temperature as the solvent, whereas acetonitrile or dichloromethane led to very sluggish or nonexistent reactions, respectively. Cleavage of primary trityl ethers was also accomplished using the same conditions in a very rapid and effective fashion. The trityl pyranosides and furanosides assayed were selectively deprotected in 2-3 h and yields higher than 85% were achieved. This reaction was also more efficient when conducted in methanol, which acts as a nucleophile to trap the generated trityl cation. 

The synthesis of losartan potassium (1) by the process research chemists at Merck is outlined in the following (Griffiths et ak, 1999 Larsen et al., 1994). Phenyltetrazole (8) is protected as the trityl phenyltetrazole 9 (Scheme 9.3). Ortho-lithiation of 9 followed by quenching with triisopropyl borate afforded boronic acid 10 after treatment with aqueous ammonium chloride. Reaction of glycine (11) with methyl pentanimidate (12) in a methanol/water mixture yielded (pentanimidoylamino) acetic acid (13), which underwent a Vilsmeier reaction with phosphorous oxychloride in DMF followed by hydrolysis to give imidazole-4-carbaldehyde 14 in moderate yield. 

Unsubstituted tetrazolyl derivative 458 was also prepared according to the following procedure (91MIP2). A solution of 5-phenyl-2-trityltetrazole in tetrahydrofuran was first treated with 1.7 M ferf-butyllithium in pentane at -25°C, in two parts. After about 30 minutes, an organolithium salt precipitated. Then a 1 M ethereal solution of zinc chloride was added to the mixture, which was then warmed to room temperature. Bis(triphenyl-phosphine)palladium(Il) chloride and 4//-pyrido[l,2-a]pyrimidin-4-one 457 were added to the reaction mixture, and after boiling for 4 hours, the 2-trityl derivative of 458 was obtained in 56% yield. Finally, detritylation with a mixture of methanol and concentrated hydrochloric acid yielded tetrazole derivative 458. 

N- Trityl a-amino acids.1 TrBr is markedly superior to TrCl for tritylation of a-amino acids. The reaction of the acids with TrBr (2 equiv.) and (excess) triethyl-amine in CHC13/DMF (2 1) provides the N-tritylamino trityl ester, which is then hydrolyzed in situ with methanol at 50°. Yields are 80-86%. 

The use of a 1% solution of iodine in methanol at 40 °C has been reported to effect the cleavage of trityl and dimethoxytrityl ethers.206 Again, the ability of solutions of iodine in methanol to release of small amounts of HI into the reaction mixture was credited. In order to further examine the role of acid in the deprotection, a variety of bases were added to the reaction mixture. In the... 

Stir the mixture at room temperature and monitor by silica TLC (solvent 20% methanol/chloroform—a slower-running spot will be observed, which will give a positive trityl test—orange spot upon dipping the TLC in dilute acid). The reaction will take up to 2 days). 

Triphenylmethanol is a tertiary alcohol and undergoes, as expected, SnI reactions. The intermediate cation, however, is stable enough to be seen in sulfuric acid solution as a red-brown to yellow solution. Upon dissolution in concentrated sulfuric acid, the hydroxyl is protonated then the portion is lost as HjO (which is itself protonated) leaving the carbocation. The bisulfate ion is a very weak nucleophile and does not compete with methanol in the formation of the product, trityl methyl ether. 

A cost effective and easily scaled-up process has been developed for the synthesis of (S)-3-[2- (methylsulfonyl)oxy ethoxy]-4-(triphenylmethoxy)-1 -butanol methanesulfonate, a key intermediate used in the synthesis of a protein kinase C inhibitor drug through a combination of hetero-Diels-Alder and biocatalytic reactions. The Diels-Alder reaction between ethyl glyoxylate and butadiene was used to make racemic 2-ethoxycarbonyl-3,6-dihydro-2H-pyran. Treatment of the racemic ester with Bacillus lentus protease resulted in the selective hydrolysis of the (R)-enantiomer and yielded (S)-2-ethoxycarbonyl-3,6-dihydro-2H-pyran in excellent optical purity, which was reduced to (S)-3,6-dihydro-2H-pyran-2-yl methanol. Tritylation of this alcohol, followed by reductive ozonolysis and mesylation afforded the product in 10-15% overall yield with excellent optical and chemical purity. Details of the process development work done on each step are given. 

Ozonolysis of 6 to produce 7 was studied at temperatures ranging from -78 to -0 °C in mixtures of dichloromethane and methanol. The intermediates that formed were found to be stable below -30 °C. Diol 7 was obtained in high yields when the reaction mixture was quenched with aqueous sodium borohydride. If the reaction mixture was warmed to room temperature before the quench, a complex mixture of products formed as indicated by the NMR spectrum. Similarly, only polymeric products were formed when the ozonolysis was carried out without methanol even at -78 °C. When ozonolysis was done at -5 to 0 °C in the presence of methanol, formation of trityl methyl ether was noticed, a result similar to which has been observed before [2], Diol 7 was obtained in near quantitative crude yield when ozonolysis was carried out below -30 °C, followed by the addition of the reaction mixture to cold, aqueous sodium borohydride solution. The product was used without further purification in the next step. 

Halogen molecules can be added to double bonds in starch derivatives, as demonstrated487 by the addition of bromine to the 2,3-double bond of 2,3-dideoxy-2,3-didehydro-6-0-trityl-starch. The reaction proceeded in methanol in the presence of silver acetate 487... 

The reaction of triphenyl methyl chloride (trityl) (A) and methanol (B)... 

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