Mesylates chlorination

Condensation of sodium phenoxide witli 2,2,2-trifluoroethyl iodide gives a product of direct substitution in a low yield, several other ethers are formed by eliminatton-addition reactions [7] Use of mesylate as a leaving group and hex amethyl phosphoramide (HMPA) as a solvent increases the yield of the substitution [S] Even chlorine can be replaced when the condensation is performed with potassium fluoride and acetic acid at a high temperature [9] (equations 6-8)... 

Activity is also retained when the hydroxyl group at the 21 position is replaced by chlorine. Reaction of corticoid 44 with methanesulfonyl chloride proceeds preferentially at the 21-hydroxyl (45) due to the hindered nature of the 11-alcohol. Replacement of the mesylate by means of lithium chloride in DMF affords clobetasol propionate (46) a similar sequence starting with the 17- butyrate ester 47, via mesylate 48, should give clobetasone butyrate, (49) [11]. 

In a similar vein, acylation of the corticoid 50 with furoyl chloride gives the diacyl derivative 51. Reduction with sodium borohydride serves to convert the 11-ketone to the alcohol 52. Hydrolysis under mild acid conditions preferentially removes the acyl group at the less hindered 21 position. The hydroxyl group in that derivative (53) is then converted to the mesylate 54. Replacement by chlorine affords mometasone (55) [12]. 

R. G. Edwards, L. Hough, A. C. Richardson, and E. Tarelli, A reappraisal of the selectivity of the DMF-mesyl chloride reagent. Chlorination at secondary positions, Tetrahedron Lett. (1973) 2369-2370. 

R. S. Bhatt, L. Hough, and A. C. Richardson, Selective chlorination of methyl p-lactoside with mesyl chloride in DMF, Carbohydr. Res., 49 (1976) 103-118. 

Synthesis of the thymidine derivative relies on the older two-step insertion of fluorine. Thus, the hydroxyl group in 3 -deoxythymidine benzoate (51-1) is first converted to the mesylate (51-2). Reaction with potassium fluoride in hydrogen fluoride replaces the mesylate by fluorine (51-3). The fact that this reaction, as that above, proceeds with retention of the configuration mles out simple displacement as the mechanism for this transform. The presence of the methyl group at position 5 negates the need for the chlorination step. Saponification then affords the antiviral agent alovudine (51-4) [52]. 

The iodo derivative is a useful intermediate for the preparation of a wide variety of different types of compounds. Primary mesyl esters also react with sodium iodide in acetone, but the selectivity of this cleavage is less because of the greater reactivity of secondary mesyl esters. oa( ) Methyl 2,3,4-tri-0-acetyl-6-0-mesyl-a-D-glucopyranoside is converted into methyl 2,3,4,6-tetra-O-acetyl-a-D-glucopyranoside with acetic anhydride and potassium acetate. Replacements of a primary mesyloxy group with fluorine by use of potassium fluoride in methanol,106 with chlorine by use of lithium chloride,102 and with pyridine to form a pyri-dinium deoxy derivative,106 have been reported. Primary tosyloxy groups have been replaced by hydrogen,106 by thiocyanate,107 and by... 

The hydroxy group of l-(2-hydroxyethyl)thieno[3,4-d]pyrimidine-2,4(3//)-dione 344 was chlorinated with thionyl chloride in a mixture of pyridine and chloroform, or mesylated with methanesulfonyl chloride in pyridine. No ring chlorination was observed under these conditions. The resulting l-(2-chloro or 2-methanesulfonylethyl) derivative 365 was cyclized to l,2-dihydrooxazolo[2,3-6]thieno[3,4-d]pyrimidin-5-one 366 with 1,8-diazabicyclo[5.4.0]undec-7-ene (DBU) (89H985). A similar transformation of 3-(2-hydroxyethyl)thieno[3,4-d]pyrimidine-2(l//),4-diones 333a,b into the 3-(2-chloroethyl) derivatives 367 with thionyl chloride occurred in chlo-... 

Since iodide ion is a strong nucleophile, the action of iodides on cellulose tosylate, mesylate, and nitrate in ketones, and chlorodeoxycellulose in DMF or 2,5-hexanedione can generate iododeoxycellulose. In use of chlorodeoxycellulose, the chlorine substituents were almost completely replaced by iodide in 2,5-hexanedione. The iododeoxycellulose thus prepared was 6-dexoy-6-iodocellulose. lododeoxycelluloses having iodo substituents at C2 and C3 were also prepared by treating various sulfonates having a DS higher than 1.0 or 6-0-trityl-2(3)-p-nitrobenzenesulfonate of cellulose with sodium iodide in DMF. Ishii [134,135] succeeded in the almost quantitative preparation of 5,6-cellulosene acetate by the treatment of acetylated 6-deoxy-6-iodocellulose (DS 0.8) with 1,8-diazobicyclo [5,4,0]undec-7-ene in DMF. 

Cesium fluoride promoted oxirane preparation starting from bis(sulfonyl fluorides) has been reported. In general, epoxide formation predominates over furan synthesis. Investigations of cyclohexane derivatives 1 show trans elimination to form 2 this still holds true when the syn chlorine is substituted by a bromine.Epoxide 4 is a versatile, general, enan-liomerically pure building block that is best synthesized by substitution of the mesylate 3. ... 

Reaction with methyl D-glycopyranosides11 1, 664, before references]. Mesyl chloride (2 equiv.) reacts with methyl a-D-glucopyranoside in DMF with selective replacement of the primary alcoholic group by chlorine to give a 6-chloro-6-desoxy-hexopyranoside. The 6-O-mesyl derivative is not an intermediate. In the case of methyl u-D-xylopyranoside (no primary hydroxyl group), 99% of unchanged glycoside was recovered from the reaction. 

Chlorination /-Butylhypochlorite. Catechyl phosphorus trichloride. N-Chlorosuccinimide. Cupric chloride. N,N-Diethyl-l,2,2-trichlorovinylamine. Iodobenzene dichloride. Mesyl chloride. Sulfuryl chloride. 

An acetonide is used as a protecting group in the synthesis of a corticoid that incorporates no fewer than four halogen atoms. The sequence starts with the conversion of the terminal hydroxyl on the side chain at C21 to a better leaving group, a mesylate, by means of methylsulfonyl chloride (30-2) (Scheme 7.30). Treatment of that intermediate with lithium chloride displaces the mesylate to afford the 21-chloro analogue (30-3). Addition of chlorine then leads to the 9a,l l)8-dichloro derivative (30-4). 

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