Trichloroethyl chloroformate

Quinoxaline with allyltributyltin and 2,2,2-trichloroethyl chloroformate (CICO2-CH2CCI3) gave bis(2,2,2-trichloroethyl) 2,3-diallyl-l,2,3,4-tetrahydro-l,4-quinoxalinedicarboxylate (17) (CH2CI2, 0°C, 3 h 30%) and a separable byproduct, bis(2,2,2-trichloroethyl) 2-aUyl-3-hydroxy-l,2,3,4-tetrahydro-l,4-quinoxalinedicarboxylate (18) (18%). ... 

The original synthesis of duloxetine (3) is relatively straightforward, involving a four-step sequence from readily available 2-acetylthiophene 30 (Scheme 14.7). Understandably, the main synthetic challenge stems from the presence of a chiral center, because duloxetine (3) is marketed as the (5)-enantiomer as shown. Thus, a Mannich reaction between 30 and dimethylamine generated ketone amine 31, which was then reduced to provide intermediate racemic alcohol amine 32. The desired optically active (5)-alcohol 32a was accessed via resolution of racemate 32 with (5)-(+)-mandelic acid, which provided the necessary substrate for etherihcation with 1-fluoronaphthalene to afford optically active amine 33. Finally, A -demethylation with 2,2,2-trichloroethyl chloroformate and cleavage of the intermediate carbamate with zinc powder and formic acid led to the desired target duloxetine (3). 

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-... 

Substituted (e.g. /7-methyl, p-t-butyl, p-chloro, and p-amino)benzoate esters of nortropine were synthesized14 by A-demethylation of the corresponding tropanyl esters with 2,2,2-trichloroethyl chloroformate. 

Trichloroethyl chloroformate, 61, 17 Tricyclo[3.3.I.l 3,7]decan-2-amine, 2-phenyl-,... 

Trichloroethyl chloroformate (96%) is commercially available from Aldrich Chemical Company, Inc., and is used without further purification. 

Hydrazine hydrate Hydrazine monohydrate (8, 9) (7803-57-8) 2,2,2-Trichloroethyl chloroformate Formic acid, chloro-, 2,2,2-trichlor-ethyl ester (8) Carbonochloridic acid, 2,2,2-trichloroethyl ester (9) (17341-93-4)... 

An excerpt from a synthesis of the phytosiderophore Nicotianamine illustrates the formation and cleavage of the 2,2,2-trichloroethyl carbonate protecting group [Scheme 4.357].676 Reaction of alcohol 357,1 with 2,2,2-trichloroethyl chloroformate and a catalytic amount of DMAP in pyridine gave the 2,2>2-tri-chloroethyl carbonate 357 2 in 98% yield. After oxidative destruction of the two p-methoxyphenyl rings to carboxylic acids and esterification, the 2224ri-chloroethyl carbonate 3573 was cleaved with zinc and acetic acid in 97% yield. 

TcecCl also TrocCl 2,2,2-Trichloroethoxycarbonyl chloride (2,2,2-trichloroethyl chloroformate)... 

Trichloroethyl chloroformate was initially used as a reagent for the introduction of the Troc group (Scheme However, there are several drawbacks to this reagent rather... 

Due to the relatively high stability of the N-2,2,2-trichloroethoxycarbonyl (Troc) group to acids and its selective removal by zinc reduction even in the presence of Al-benzyloxy-carbonyl derivatives, it can offer interesting possibilities in the syntheses of particular pep-tidic compounds for example, it has been used for N -protection of lysine in the synthesis of The Af -Troc-protected lysine is readily prepared by reaction of the copper(II) complex with 2,2,2-trichloroethyl chloroformate (Troc-Cl)h d or by reaction of Z-Lys-OH (obtained via the benzylidene route, see Section 2.1.2.2.1.3) with 2,2,2-trichloroethyl chlor-oformate.f ... 

N-Alkylated norcocaine derivatives, e.g. N-allyl-, N-dimethylallyl-, A -cyclo-propylmethyl-, and N-(3-butenyl)-norcocaine, were prepared and examined for cocaine-like activity. Cocaine was demethylated with 2,2,2-trichloroethyl chloroformate, followed by reduction in acidic medium, and subsequently N-alkylated. 

A semisynthesis of the 19-hydroxy taxol derivative, 19-hydroxy docetaxd 869, was accomplished by semisynthesis of a new baccatin derivative, lO-deacetyl-19-hydroxybaccatin III 866, which, after temporary protection at positions C-7, C-10, and C-19 with Troc groups using 2,2,2-trichloroethyl chloroformate (Troc-Cl) (to give 867), was coupled with N-Boc-N,0-isopropylidene-phenylisoserine 868 to yield 869 [629]. Analogue 869 exhibits a high level of in vitro cytotoxicity and thus the results demonstrate that chemical modifications at C-19 can be made without significant loss of biological activity. 

Trichloroethyl chloroformate (Troc-Cl) has been used for the 0-protection of the C-7, C-10, and C-19 positions of lO-deacetyl-19-hydroxybaccatin III 262, a novel baccatin derivative which is reacted with the N-Boc-3-phenylisoserine 264 in the presence of DCC/DMAP to form, after further steps, the novel 19-hydroxy-docetaxel 265 [192], The analogue 265 exhibits a high level of in vitro cytotoxicity... 

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