1.1- Dimethyl-2,2,2-trichloroethyl

Dimethyl-2,2,2-trichloroethyl, 181 2-(Trimethylsilyl)ethyl, 182 2-(Phenylsulfonyl)ethyl, 182 2-(Triphenylphosphonio)ethyl, 183 Isobutyl, 183 Vinyl, 183 Allyl, 184... 

Six protective groups for alcohols, which may be removed successively and selectively, have been listed by E.J. Corey (1972B). A hypothetical hexahydroxy compound with hydroxy groups 1 to 6 protected as (1) acetate, (2) 2,2,2-trichloroethyl carbonate, (3) benzyl ether, (4) dimethyl-t-butylsilyl ether, (5) 2-tetrahydropyranyl ether, and (6) methyl ether may be unmasked in that order by the reagents (1) KjCO, or NH, in CHjOH, (2) Zn in CHjOH or AcOH, (3) over Pd, (4) F", (5) wet acetic acid, and (6) BBrj. The groups may also be exposed to the same reagents in the order A 5, 2, 1, 3, 6. The (4-methoxyphenyl)methyl group (=MPM = p-methoxybenzyl, PMB) can be oxidized to a benzaldehyde derivative and thereby be removed at room temperature under neutral conditions (Y- Oikawa, 1982 R. Johansson, 1984 T. Fukuyama, 1985). 

Dimethyl Acetals and Ketals 3. Bis(2,2,2-trichloroethyl) Acetals and Ketals... 

Methyl Carbamate 5. 9-Fluorenylmethyl Carbamate 8. 2,2,2-Trichloroethyl Carbamate 11. 2-Trimethylsilylethyl Carbamate 16. 1,1-Dimethylpropynyl Carbamate 20. 1-Methyl-1-phenylethyI Carbamate 22. 1-Methyl-l-(4-biphenylyl)ethyl Carbamate 24. 1,1 -Dimethy 1-2-haloethyl Carbamate 26. l,l-Dimethyl-2-cyanoethyl Carbamate 28. r-Butyl Carbamate... 

The nature of the aromatic substituents is apparently not critical for SSRI activity, as indicated by the structure of duloxetine (23-5), where one ring is replaced by thiophene and the other by naphthalene. The synthesis starts as above by the formation of the Mannich base (23-1) from 1-acetyl thiophene with formaldehyde and dimethyl-amine. Treatment of that intermediate with the complex from lithium aluminum hydride and the 2R,3S entantiomer of dimethylamino-l,2-diphenyl-3-methyl-butane-2-ol gives the S isomer (23-2) in high enantiomeric excess. Treatment of the aUcoxide from (23-2) and sodium hydride with 1-fluoronaphthalene leads to the displacement of halogen and thus the formation of ether (23-2). The surplus methyl group is then removed by yet another variant of the von Braun reaction that avoids the use of a base for saponifying the intermediate urethane. Thus, reaction of (23-3) with trichloroethyl formate leads to the A -demethylated chlorinated urethane (23-4). Treatment of that intermediate with zinc leads to a loss of the carbamate and the formation of the free secondary amine duloxetine (23-5) [23]. 

Chloro-3,3-dimethyl-2-(2, 2, 2 -trichloroethyl)cyclobutanone Typical Procedure 33... 

SYNTHESIS (from 5-MeO-DMT). To a solution of 0.10 g 5-methoxy-N,N-dimethyl tryptamine (see 5 MeO-DMT) in 5 mL benzene there was added 0.5 g 2,2,2-trichloroethyl chloroformate, and the resulting solution was held at reflux temperature for 2 days. After cooling there was added 5 mL Et20 and the organic phase washed with 2x20 mL 3N HCI followed by 20 mL H20. The solvent was then removed under vacuum. The residue (N-... 

Organophosphorus pesticides are specific efficient contact and systemic (acting inside a plant) insecticides and acaricides. Among them are 0,0-dimethyl-(l -hydroxy-2,2,2-trichloroethyl)phosphonate (trichlorfon, or... 

Trichlorfon can be synthesised in three stages the preparation of trichloroacetic aldehyde (chloral) the production of 0,0-dimethyl ether of phosphorous acid (dimethylphosphite) the synthesis of 0,0-dimethyl(l-hydroxy-2,2,2-trichloroethyl)phosphonate (trichlorfon). 

Mori and Tsuji651 have observed that, upon addition of LiCl as cocatalyst to the above system, the reaction takes a different route and the major product is a 1 2 adduct. For example, methyl acrylate with CC14 (4,4 molar ratio) in acetonitrile at 170 °C after 16 hours yielded mainly dimethyl 2-chloro-4-(2,2,2-trichloroethyl) glutarate (equation 87) ... 

The synthesis of BENZYL ISOCYANIDE from benzaldehyde via reductive amination with 5-aminotetrazole followed by oxidation of the resultant amine with sodium hypobromite provides a general method for the synthesis of isocyanides. The preparation of BIS(2,2,2-TRICHLOROETHYL) AZODICARBOXYLATE makes available an alternative to dimethyl azodicarboxylate that is not only more reactive in Diels-Alder reactions but whose ester groups can be removed under neutral conditions. 

Protection of aldehydes and ketones. Treatment of a dimethyl or diethyl acetal with 1.5 eq. of trichloroethanoi in refluxing benzene under acid cataly.sis (p-TsOH) gives the mixed acetal use of 4 eq. of the alcohol gives the di-2,2,2-trichloroethyl acetal. 

Racemic isomers of a-cyano-3-phenoxybenzyl cis-2,2-dimethyl-3-(2,2,2-trichloroethyl)cyclopropanecarboxylate (64) were isomerized to 65 at the a-position by heating in /-propanol in the presence of DBU (81GEP3008986). 

Thus, [2-1-2] cycloaddition of 2-methylpropene with chloro(2,2,2-trichloroethyl)ketene (prepared in situ from 2,4,4,4-tetrachlorobutanoyl chloride and triethylamine) in cyclohexane yielded 2-chloro-3,3-dimethyl-2-(2,2,2-trichloroethyl)cyclobutanone (70%). This a-chloro-cyclobutanone undergoes a stereoselective cine rearrangement in the presence of triethylamine in refluxing toluene for 20 hours to give cw-(2a,4a)-2-chloro-3,3-dimethyl-4-(2,2,2-tri-chloroethyl)cyclobutanone in 94% yield,which was resolved by means of the diastereomeric salts of their sodium hydrogen sulfite adducts with ( —)- or (- -)-l-phenylethylamine. ... 

Dichlorovos may be prepared in several ways. Methanol is treated with chloral (CCI3-CHO) and PCI3 to get dimethyl-l-hydroxy-2,2,2-trichloroethyl phosphate (55), which is heated with 25% NaOH to yield dichlorovos (23) [60]. Alternatively, chloral alcoholate (56), the precursor of chloral prepared by passing chlorine into cooled ethanol, is allowed to react with (MeO)jP to form dichlorovos [61]. In another approach, methanol is treated with PCI3 to get (MeO)3P (57) [62]. This reaction may also be carried out in the presence of CuCl at - 10 C to yield the adduct (MeO)3P.CuCl (58) [63]. Reaction of 57 or 58 with chloral yields dichlorovos (23) [62,63]. 

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