Methyl bromoacetate

Chloro-2-(ethoxycarbonyl)-3-(4-fluorophenyl) N-[5-Chloro-2-(4-fluorobenzoyl]benzamide, methyl bromoacetate (1) NaH (2) NaOMe 30 [2]... 

In a 1-1, three-necked, round-bottomed flask equipped with a calcium chloride drying tube, a mechanical stirrer, and a ground-glass stopper are placed 28.2 g. (0.184 mole) of freshly distilled methyl bromoacetate, 500 ml. of anhydrous iV,iV-dimethy]acetamide (Note 1), and 20.0 g, (0.168 mole) of methyl nitroacetate (Note 2). The solution is stirred vigorously while 146 ml. (0.168 mole) of 1.15N sodium methoxide in... 

Difluoronitroethanol m aqueous alkaline solutions reacts readily with methyl bromoacetate [/] and with epoxides [2] (equation 1)... 

A treatment of 2-butyltelluroaniline with an equimolar amount of bromoacetic acid results in spontaneous cyclization of the formed telluronium salt 31 to give 1-butylbenzotellurazinonium bromide 30. That the alkylation occurs at the tellurium and not at the nitrogen atom of 2-butyltelluroaniline has been proved by the isolation of the methyl ester of 31 in 60% yield when the amine was coupled with methyl bromoacetate under the same reaction conditions. Elimination of butyl bromide from 30 readily occurs on heating of its DMF solution leading to 2//-l,4-benzotellurazin-3(4//)-one 32 in 90% yield. 

Methoxytrimethylsilane, 123 Methyl acetoacetate, 92 Methyl bromoacetate, 107 Methyl 11-hydroxyundecanoate, 58 Methyl lithium, 27,28 Methyl 10-undecenoate, 58 2-Methyl-l, 3-dithiane, 81 (fl/ ,5 )-Methyl-3-phenyldiniethyl-silyl-3-phenylpropionic acid, 53-4 2-Methyl-3-Phenylprop-2-cnal, 111 2-Methyl 2-lrimethylsilyl-1,3-dithiane, 81 2-Methyl-l-(trimcthylsilyloxy)cyclo-hex-l-ene, 100,109 2-Melhyl-l-lrimethylsilyloxy)cyclo-hcx-6-enc, 100 2-Methyl-2-trimethylsilyloxy-pentan-3-one, 132 2-Methylacetophenone, 42-3 2-Methylbutyraldehyde, 85 2-Methylcyclohexanone, 99,100 2-Methylcyclohexanone, 131 4-Methyldec-4-ene, 67-8 Methylenation, 63 2-Methylpropen-l-ol, 131 Methyltriphenylphosphonium bromide, 27 Michael addition, 85 Monohydridosilanes, 128 Monohydroalumination, 29... 

A mixture of finely ground benzyltrimethylammonium fluoride (125 mmol) and molecular sieves (50 g, 4 A) in THF (50 ml) was stirred for 14 h at ambient temperature, and then the mixture was cooled to 0°C. A solution of l-(trimethylsilyloxy)cyclohexene (115 mmol) and methyl bromoacetate (105 mmol) in THF (50 ml) was added with stirring over 10 min. After stirring for a further 10 min at 0 °C, stirring was continued for 11 h at ambient temperature. The reaction mixture was filtered through Celite. concentrated and distilled, to give the ketoester (75 mmol, 65%), b.p. 90-100°C/1.2mmHg. 

The same elimination strategy was used for the synthesis of the natural product (i )-(-)-dysidazirine 15 as is shown in Scheme 10 [23]. The requisite aziri-dine ester was prepared by treatment of sulfimine 19 with the lithium enolate of methyl bromoacetate. This reaction is a Darzens-type condensation leading to czs-M-sulfinylaziridine ester 20. The elimination of sulfenate was accomplished in the same manner as mentioned above (see Scheme 9). The natural product 15 (see Fig. 1) was obtained in 42% yield. Attempts to prepare azirinomycin 14 in a similar fashion all failed [23]. 

CsHgNOj Ethyl nitrite CaHjBrOg Methyl bromoacetate... 

With the A-ring unit readily available, we directed our attention to the formation of the B-ring. At first, we duplicated the five step scheme reported in Sih s strigol synthesis involving 1) esterification of the acid 14, 2) allylic bromination with N-bromo 8 ucc i n imi d e (NBS) to 15, 3) condensation with the sodium salt of dimethyl malonate to 16, 4) alkylation with methyl bromoacetate to 17, and 5) acid catalyzed hydrolysis and decarboxylation to the acid 18. 

A rich family of 2-alkoxycarbonyl-l,3,2-oxazaphospholidine-2-oxides 179-181 was prepared from the reaction of camphor derived aminoalcohols 177 and 178 with either methoxycarbonyl phosphonic dichloride or ethyl dichlorophosphite followed by the reaction with methyl bromoacetate. The reaction with aminoalcohol 177a afforded the phosphorus epimers 179 and 180, in ratios from 1/1 to 12/1 depending on the iV-substituent which could be separated easily by column chromatography. The reaction with aminoalcohols 178a-c, however, gave a single epimer 181a-c in each case (Scheme 50) [81]. 

Another example with porphyrinic dipolar species uses pyridinium salt derivatives as precursors of porphyrinic pyridinium ylides (Scheme 18) <05TL5487>. The procedure involves the reaction of porphyrin 58 with methyl bromoacetate, in refluxing chloroform, to give pyridinium salt 59. The latter, in the presence of K2CO3, reacts with 1,4-benzoquinone to yield only the mono-addition compound 60. Notably, when the reaction was performed in the presence of DBU, bis-addition occurred and the porphyrinic dimer 61 was the only isolated addition product. 

Deprotonation of 3,3-bis(l-methylimidazol-2-yl)methane (41) with nBuLi at the bridging carbon atom and subsequent reaction with methyl bromoacetate gives methyl 3,3-bis(l-methylimidazol-2-yl) propionate bmipme (42) in high yields. Saponification of bmipme with aqueous NaOH gives bis-3,3-(l-methylimidazol-2-yl)propionate (bmip)... 

Method D - using dibutyl telluride (typical procedure). A mixture of 3-nitrobenzalde-hyde (0.38 g, 2.5 mmol), methyl bromoacetate (0.38 g, 2.5 mmol) and dibutyl telluride (0.61 g, 2.5 mmol) is refluxed in THF. After 6 h, the mixture is worked up as for method C to give pure ( )-methyl 3-(3 nitrophenyl)propenoate (0.460 g (89%)). 

Method E - catalytic procedure (typical procedure). Benzaldehyde (106 mg, 1.0 mmol), methyl bromoacetate (165 mg, 1.1 mmol), triphenyl phosphite (356 mg, 1.2 mmol), dibutyl telluride (48 mg, 0,2 mmol), KjCOj (179 mg, 1.3 mmol) and THF (4 mL) are mixed and stirred at 50°C for 13 h (monitored by TLC). The reaction mixture is filtered rapidly through a small amount of SiOj with EtOAc as the eluent to remove inorganic salts and dibutyltellurium oxide. Preparative TLC with EtOAc/petroleum ether at 60-90°C (1 9) as the eluent yields 3-phenylpropenoate (160 mg (98%)). 

Rolgamidine (14) is a dihydropyrrole derivative which has anndiarrheal activity It can be synthesized by alkylation of trans 2,5-dimethyl-3 pyrroline (12) with methyl bromoacetate to give 13 An amide-ester exchange reaction with guanidine hydrochlonde completes the synthesis of rolgamidine (14) [3]... 

In general, alkylations as well as some acylations of enamines using halides as the leaving group occur predominantly on carbon (B-69MI20700). For example, treatment of A2-piperideine (115) with methyl bromoacetate followed by sodium borohydride reduction... 

Employing the same reaction conditions the addition of methyl bromoacetate, t-butyldimethylysilyloxyethyl bromide or chlorotrimethylsilane as electrophile afforded the corresponding a-functionalized N-dialkylaminolactams 79 and 81. Auxiliary removal in the latter case to form 82 again led to a partial racemization (ee = 83%) (Scheme 1.1.23). 

Miscellaneous Compounds. A saturated spirocychc pyrrohdine serves as the nucleus for a diamine that has been described as a hypohpemic agent. Treatment of the carbanion of the substituted cylcohexane carboxyhc ester (20-1) with methyl bromoacetate leads to the alkylation and formation of the diester (20-2). Saponification of the ester groups followed by reaction with acetic anhydride leads to ring closure of the succinic anhydride (20-3). Condensation with ammonia leads to the succinimide (20-4). The side chain is then added by alkylation of the anion on nitrogen with l-bromo-4-dimethylaminobutane (20-5). Reaction of this last intermediate with lithium aluminum hydride leads to the reduction of the carbonyl groups to methylene. This affords the pyrrolidine (20-6) atiprimod [22]. 

A successive refinement (MNDO-PM3) of the reaction of the Reformatsky derivative of methyl bromoacetate with both formaldehyde and methanimine was carried out including coordinated THF molecules. It identified a twist-boat transition structure as the most stable TS for the transformation of G into H7. 

To better compare modern protocols for the Reformatsky reactions, hereinafter discussed in this section, it is interesting to read, as an example, the experimental procedure reported by R. B. Woodward and coworkers in 1956 for the synthesis of the Lysergic acid precursor 3 (equation 2)14. The procedure adopted was a Barbier-like protocol, involving the addition of Zn and of methyl bromoacetate (la) in three portions to a solution of 2 in hot benzene. 

We read in the experimental section A mixture of 300 g of 1-benzoyl-5-keto-l,2,2a,3,4,5-hexahydrobenz[cd]indole (2), 300 g of activated zinc, 1.0 g of mercuric chloride, 6 L of dry benzene and 90 g of methyl bromoacetate (la) was prepared in a 12 L, 3-neck flaskfittedwith a stirrer, reflux condenser and heating mantle. The mixture was heated under reflux and stirred, and after an induction period of 10-30 minutes the reaction started, and the solution became cloudy. After 3.5 hours 90 g of methyl bromoacetate and 20 g of zinc were added, and after five hours, 75 g of the bromoester and 60 g of zinc were added. Refluxing and stirring were maintained for a total of six hours, after which the reaction mix was allowed to cool and stand overnight . 

A synthesis of a higher sugar, 2-deoxy-4-octulose, has been carried out using, as the key step, the Reformatsky reaction of methyl bromoacetate (la) with the /i-D-arabino-hexos-2-ulopyranose derivative 36, which affords the manno-derivative 37 in good d.e. (equation 26)102. The same authors developed analogous diastereoselective syntheses of... 

A nickel-catalysed electro-Reformatsky reaction has been previously presented (Section . . , Figure 5)57. Based on a formally related catalytic cycle, a nickel-catalysed 3-component route to /J-arnino esters and amides has been proposed (equation 41). To a CH2CI2 solution of an aldehyde and an aromatic amine are successively added dimethylz-inc, methyl bromoacetate (la) and bistriphenylphosphine nickel dichloride. After 1-3 h at rt, products were isolated in very high yield, and this procedure was exploited for the preparation of a chemical library of 64 members, using 4 aldehydes, 4 cr-haloesters and 4 substituted anilines58. 

Methyl acrylate, 58, 82 Methylallyl, chloride, 57, 36 p-Methylbenzenesulfonyl cyanide, 57, 89 Methyl bromide, 58,43 Methyl bromoacetate, 57, 60 Methyl carbazate, 58, 102, 103,106 Methyl chloride diphenyl-, 55, 94 Methyl chloride polystyrene, 56, 96 2-Wethylcyclohexanone, 57, 70 2-Methyl-2-cvclohexenone, 58, 158, 159, 162, 163... 

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