Conversion of hydroxy group in certain alcohols into fluorosulfonate ester or trifluoromethylsulfonate ester

A technology of perfluoroalkyl sulfonate and fluorosulfonate, which is applied in the preparation of sulfonate ester, organic chemical method, sulfuric acid ester preparation, etc., can solve the problem of difficult preparation of acid anhydride, toxicity, and high cost of trifluoromethanesulfonic acid And other issues

Inactive Publication Date: 2001-07-11
汉斯·雅各布·埃德加·勒文塔尔 +1
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  • Summary
  • Abstract
  • Description
  • Claims
  • Application Information

AI Technical Summary

Problems solved by technology

The main problem is the high cost of trifluoromethanesulfonic acid, especially when considering that for the preparation of trifluoromethylsulfonate esters (or salts), one has to use an anhydride made from two molecules of the acid, of which only one Participate in esterification
However, there is no method for performing this reaction in the prior art
Anhydride itself is difficult to prepare, volatile and toxic (same level as phosgene)
Danger aside, currently offered sales prices make fluorosulfonation more than 200 times more expensive than tosylation

Method used

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  • Conversion of hydroxy group in certain alcohols into fluorosulfonate ester or trifluoromethylsulfonate ester
  • Conversion of hydroxy group in certain alcohols into fluorosulfonate ester or trifluoromethylsulfonate ester
  • Conversion of hydroxy group in certain alcohols into fluorosulfonate ester or trifluoromethylsulfonate ester

Examples

Experimental program
Comparison scheme
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Embodiment 3

[0038] Note: N-methylsulfamoyl chloride and N,N-dimethyl analogs described in the following examples are given by G.Weiss and G.Schulze, Liebig's Ann.Chem.1969,729,40, General method preparation, productive rate is more than 95%, and this method is after adding the titanium tetrachloride of catalytic amount (1ml), utilizes the water bath of constant temperature control and the gas catcher drawn by condenser, heats corresponding under reflux A suspension of amine hydrochloride (1 g.mol.), sulfonyl chloride (2.1 g.mol.) and acetonitrile (200 ml) for 1.5 times the time necessary for complete dissolution. In the case of the N-methyl compound, this took more than 72 hours, whereas it took less than 8 hours with the N,N-dimethyl chloride (the latter being commercially available). Then, after solvent removal, the product was distilled by bulb-to-bulb method (ice-cooled collector) below 0.5 mmHg (heat bath or oven below 130°C). N-methylsulfamoyl chloride is distilled at 70-75°C / 0.1mm...

Embodiment 4

[0041] Trifluoromethanesulfonic acid (10.88 g, 72 mmol) was added to dry CCl of the sulfamoyloxy compound (16.81 g, 74.71 mmol) prepared in Example 2 under vigorous stirring at 0 °C 4 (40 mL) solution, and stirring was continued at room temperature for 8 hours. The resulting N,N-dimethylsulfamic acid was filtered off and washed with CCl 4 Wash the filtrate with cold 0.5 M NaHCO 3 Wash, dry and remove solvent at room temperature 23 mmHg. Fractional distillation (Teflon column) residue, to obtain triflate (or salt) 12.94g (yield 71.5%), boiling point 32-34 ℃ / 0.07mmHg, n.m.r.1.31 (t, 3H), 1.67 ( d, 3H), 4.28(q, 2H); i.r. 1767, 1428, 1217, 1153, 961, 622; [α] 21 :+43.7 0 .H.H.Paulsen, P.Himpkamp, ​​and T.Peters, Liebigs Ann.Chem.1986,664, Utilize trifluoromethanesulfonic anhydride-pyridine to prepare S-enantiomer, reported boiling point is 40.5°C / 0.9mmHg, [α ]:-40 0 ; while the commercially available S-enantiomer has a reported boiling point of [α]-44 0 ±2. Example 5 Ethyl...

Embodiment 5

[0042] Fluorosulfonic acid (6.1 g, 61 mmol) was added to dry CCl at 0 °C 4 Of the sulfamoyloxy compound prepared in Example 2 (13.55 g, 60.22 mmol) in (35 mL), the whole mixture was stirred vigorously at room temperature for 7 hours. Treat according to Example 4, and distill (boiling point is 34-36 ℃ / 0.1mmHg) to obtain product, yield is 9.23g (82%), n.m.r.1.31(t, 3H), 1.56(d, 3H), 4.25(t, 2H),5.19(q,1H), 19 Fn.m.r.: singlet at 98.96 p.p.m; i.r.1760.5, 1447, 1224, 980, 839; [α] 16 :+44.34 0 , there is no high-resolution [M + ]peak. Conversion experiment example 6 Preparation of ethyl S-2-acetoxypropionate from R-trifluoromethylsulfonate (or salt)

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Abstract

The present invention provides a method of converting a hydroxy group in alcohols containing an electron withdrawing group into perfluoroalkanesulphonate (or salt) and fluorosulphonate esters (or salt), which are good leaving groups, with inversion of configuration where the hydroxyl-bearing carbon is chiral. The method consists of converting said alcohol to an O-N,N-dialkylsulphamate ester (or salt) and reacting said O-N,N-dialkylsulphamate ester (or salt) with a perfluoroalkanesulphonic acid or fluorosulphonic acid. Such a method is useful for preparing chiral compounds for pharmaceutical and agrochemical use.

Description

field of invention [0001] The present invention relates to the field of organic chemistry. More specifically, the present invention provides novel methods for converting hydroxyl groups in certain alcohols into good leaving groups with concomitant configuration inversion wherein the carbon bearing the hydroxyl group is chiral. This method is especially useful for the preparation of chiral compounds for pharmaceutical and agrochemical applications. Background of the invention [0002] Government regulations in many countries, especially in the United States, address the need to find economical methods of producing the more active enantiomers of drugs whose molecules are chiral, other than by resolution of racemic end products (or intermediates) , not by utilizing expensive chiral catalysts or coagents - often non-recyclable or partially recyclable - nor by enzymatic processes. To meet this necessity, three requirements must be met [see A.N. Collins, G.M. Sheldrake, and J. C...

Claims

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Application Information

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Patent Type & Authority Applications(China)
IPC IPC(8): C07C303/24C07C303/26C07C303/34C07C307/02C07C309/65C07C309/84
CPCC07B2200/07C07C303/24C07C303/26C07C303/34C07C305/26C07C307/02C07C309/65
Inventor 汉斯·雅各布·埃德加·勒文塔尔罗恩·本杰明·勒文塔尔
Owner 汉斯·雅各布·埃德加·勒文塔尔
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