Sarcosine, ethyl ester

Intramolecular cycloadditions of 4/f-pyrido[l,2-n]pyrimidin-4-ones 235 (R = H, Me Ph) and MeNHOH HCl gave tetracyclic isoxazolo derivatives 237. In the case of 235 (R = Me) a minor epimer 238 was also isolated (00JCR(S)414). Similar reaction of 235 (R = H, Me, Ph) and sarcosine ethyl ester HCl afforded an isomeric mixture of epimeric tetracyclic pyrrolo derivatives 239 and 240. In the reaction of 235 (R = H) and PhCHjNHCHjCOOEt only one product 241 was obtained. 

Vinamidinium salts have been used for the preparation of 2,3- or 2,5-disubstituted pyrroles. Thus, reaction of sarcosine ethyl ester with 18 results in an amine-exchange reaction at the least hindered position. Anion mediated cyclization and elimination of dimethylamine leads to 19 <96T6879>. 

The central five-membered ring of Manzamine A (315), a member of a family of antileukimic and antibacterial marine polycyclic alkaloids, has been constructed using intramolecular azomethine ylide technology (88). Model studies on the construction of the central ABC rings, by condensation of the aldehyde 316 prepared by standard chemistry with sarcosine ethyl ester, furnished the desired ABC ring system as a single diastereoisomer in 45% yield (Scheme 3.105). 

The synthesis of pyrrolo[2,3- 7 pyridazines can be achieved by starting either with pyridazine, a tetrazine, or a pyrrole. Pyridazinone 80 reacts with bromomethyl derivatives to give poor yields of 81 <1996H(43)1863> (Equation 34), while 5-acetyl-2-methyl-4-nitro-6-phenyl-3(2//)-pyridazinone, after treatment with sarcosine ethyl ester for a brief time at room temperature, followed by acid hydrolysis afforded a good yield of 82 (70%) <1994S669>. 

Amino acid derivatives react with C6o both thermally and photochemically to yield different products. Gan et al. intensively studied the photochemical reactions of C6o and amino acid derivatives such as sarcosine esters, glycine esters, and iminodiacetic esters [268], The thermal reaction of the sarcosine ethyl ester 98 led to the formation of a 4 1 mixture of two products, the major being compound 99 and the minor being compound 100 containing two ester functionalities (Scheme 43). 

Tetra-O-acetyl-D-glucosyl bromide (4.1 g.) and sarcosine ethyl ester (2.4 g.) were warmed together on a waterbath at 50° and the mixture became dark-brown. The sirup was kept at room temperature for 20 hours, whereupon crystals formed. Dry ether was added, sarcosine ester hydrochloride was removed by filtration, and the solution was quickly washed with water and dried. Removal of the ether gave a yellow sirup which, on treatment with methanol, gave needles of tetra-O-acetyl-iV-D-gluco-sylsarcosine (3.5 g., 79% yield) after recrystallization from methanol, m.p. 87-88° (no dec.). This compound was treated at 0° with methanol (100 ml.) saturated with ammonia. After removal of the solvent, crystals of A-D-glucosylsarcosine (1.7 g., 88% yield), m.p. 169-170°, were obtained. 

Heating the 1,1 -disubstituted alkene with excess sarcosine ethyl ester in xylene with molecular sieves in a sealed tube at 180°C (7 h) afforded (60) (40%) (Equation (31)) <84JA7i75>. This product was then processed in two steps to (+ )-Sceletium alkaloid A4. 

Sarcosine ethyl ester hydrochloride (1.0 mmol) was suspended in 1ml DMF, treated with triethylamine (1.1 equiv.) and the Step 2product (1.0 mmol), then stirred overnight. The solution was quenched with 10 ml water, then extracted three times with 10 ml chloroform, dried over Na2S04, and concentrated. The residue was coevaporated four times with ethyl alcohol and the product isolated in 95% yield as a white foam. 

A similar reaction sequence condenses iV-cyanoiminodithiocarbamic esters (7) with a-cyanoammonium salts (e.g. sarcosine nitrile sulfate) (Scheme 2.3.2). The isothiourea product (8) readily cyclizes to give 4-amino-5-cyanoimidazoles when heated with sodium ethoxide in DMF solution. It is possible to convert the dithiocarbamic esters directly into imidazoles if they are heated in DMF solution with sarcosine ethyl ester hydrochloride or methylaminoacetophenone in the presence of triethyamine [3]. These direct cyclizations arc, however, examples of both 1,2 and 1,5 bond formation. (See also Section 3.2). 

Dihydro-2H-pyran-5-carbaldehyde (/) was treated with sarcosine ethyl ester (2) in the presence of sodium ethoxide. What is the structure of the crystolline product CiiHigNOa given its NMR spectra 22 ... 

The preparation of two of the three possible isomeric thieno-1,2-thiazin-4-ones (Schemes 5 and 6)128 involved reactions reported12 for the corresponding benzothiazines (see Scheme 1 ). Thus, methyl 3-chlorosul-fonylthiophene-2-carboxylate (152) with sarcosine ethyl ester gave thiophene sulfonamide (153) which, with methanolic sodium methoxide, yielded 3-methoxycarbonyl-4-hydroxy-2-methyl-2H-thieno[2,3-c]-l,2-thiazine 1,1-dioxide (154). Heating 154 with 2-aminothiazole gave 155, a thieno-1,2-thiazine analog of sudoxicam (20) (Scheme 5). 

Chloro-2-diben2oylaminobenzyl bromide Sarcosine methyi ester Ethyl chloroformate... 

Most published information deals with the analysis of sarcosine derivatives. Sarcosine is often made by reaction of chloroacetic acid with methylamine. M-acylated sarcosine is made by reaction of the acyl chloride with sarcosine in the presence of alkali. Possible impurities in the final product thus include glycolic acid and Ai-methylalkylamide. Fatty acid and chloride salts are expected as byproducts of the acylation reaction, and ethyl esters of fatty acids and acylsarcosine may be formed during workup of the synthesis product with ethanol (137). 

Nonionic impurities include ethyl esters of the fatty acids and acylsarcosine resulting from workup of the reaction mass with ethanol. They also include the acylation products of any methylamine contaminating the sarcosine raw material. 

According to Eq. (11), Confalone has presented a new method of generation of azomethine ylides through the condensation of N-substituted ot-amino esters with aldehydes (83JOC2994 84JA7175). Thus, 5-formylmethyldibenzo-[a.d]tropylidene or o-(allyloxy)benzaldehyde is heated with ethyl sarcosinate or methyl prolinate under reflux in toluene. The water formed is continuously driven off with the aid of a Dean-Stark trap. The ester-stabilized azomethine ylide 77 or 78 quantitatively generated is trapped in an intramolecular fashion. 

In cases of ethyl AT-methyl-A,-(3-nitro-2-pyridyl)aminoacetates 5 with a tertiary amino nitrogen as the corresponding sarcosine ester, treatment with bases such as sodium ethoxide or potassium carbonate in ethanol produces 4-alkyl-l-hydroxypyrido[2,3-b]pyrazine-2,3(l/f,4//)-diones 6 as the principal products in low yield.8 9... 

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