N-(Methoxymethyl)-N-(trimethylsilylmethyl)benzylamine

N-(Methoxymethyl)-N-(trimethylsilylmethyl)benzylamine is clear colorless to light yellow liquid

To the solution of formaldehyde (37percent, 16.816 g, 207.19 mmol) at 0°C N-benzylo- 1 -(trimethylsilyl)methanamine (Intermediate P15, 28.588 g, 144.89 mmol) was added dropwise. To the mixture solid potassium carbonate (16.182 g, 115.91 mmol) was added and the whole was stirred at room temperature for 2 hours. Water (50 ml) was added and the mixture was extracted with diethyl ether (2 x 50 ml). Organic layer was washed with brine and dried over sodium sulphate. Solvent and drying agent were removed to obtain 33.551 g of the title product in the form of a yellow oil (yield 97.5percent). In a 2L multi-bottle, add 1282.0g (6, 6mol)Benzyltrimethylsilylmethylamine, 800 mL (38 lmol)Formaldehyde and 328 mL (38. lmo 1) methanol, 0 ° C under stirring 1 h, And then control the temperature at 10 ° C ~ 15 ° C stirring 3h, To the mixture Was added 413.0 g (2.9 mol) of potassium carbonate, After returning to room temperature and stirring overnight, Filter, filter cake with ether, Collecting filterLiquid, the organic phase is separated, the organic phase is pressurized and concentrated, To give 1530.5 g of benzylmethoxymethyltrimethylsilylmethylamine as a yellow oil, Yield 91percentN-(Benzyl)-N-(methoxymethyl)-N-(trimethylsilylmethyl)amine (Scheme 3, 3-4); To a solution of chloromethyltrimethylsilane (1.34 kg, 10.96 mol) in acetonitrile (17.0 L) is added benzylamine (2.34 kg, 21.92 mol) and the reaction mixture is heated at reflux for 16 h. The reaction mixture is cooled to room temperature and the precipitate of benzylamine hydrochloride is removed by filtration. The filtrate is concentrated under vacuum to about 5 L and then diluted with water (5 L). The reaction mixture is extracted with hexane (2.x.5 L). The organic extracts are combined and washed with brine (5 L) and dried over MgSOTo a mixture containing 6.2 mL of aqueous formaldehyde (37percent) and 3.9mL of methanol at 0°C, the amine iii (12.0 g, 62.1 mmol) was slowly added (30 min).The temperature was then raised to 25°C and the reaction was stirred for 4h. Thereaction was quenched with a saturated solution of K2CO3 and extracted withdichloromethane (4x50 mL). The organic phase was dried with anhydrous Na2SO4, filtered and the solvent removed under vacuum. The residue was distilled under highvacuum at 120°C, and the product 1 was obtained as a colorless liquid in 64percent yield(9.50 g, 39.9 mmol).1H NMR (CDCl3, 400.15 MHz) δ (ppm): 0.05 (br.s, 9H), 2.19 (s, 2H), 3.24 (s, 3H), 3.77 (s, 2H ), 4.01 (s, 2H), 7.18-7.35 (m, 5H).13C NMR (CDCl3, 100.4 MHz) δ (ppm): -1.47, 42.8, 55.4, 59.4, 88.4, 126.8, 128.1, 139.7.Synthesis of benzyl(methoxymethyl)trimethylsilanylmethylamine (Reaction with 1.3 eq. of Paraformaldehyde) To a solution of chloromethyltrimethylsilane(13.4g, 0.11mol) in CH3CN (100mL) was added benzylamine (23.45g, 0.22mol) and the reactionmixture was heated at reflux for 16h. The reaction mixture was cooled to room temperature , andthe precipitate of benzylamine hydrochloride was removed by filtration. The filtrate wasconcentrated under vacuum and the residue was diluted with water (50mL).The reaction mixturewas extrated with PE (50mL*2 ).The organic extracts were combined and washed with water(50mL*2) and brine (50mL) and dried over Na2SO4. The filtrate was concentrated under vacummto give 18.8g crude product. 88.9percent Yield. The above-mentioned crude product (18.8g0.098mol)was added to a mixture of 37percent formaldehyde (9.49g 0.118mol)and methanol (3.78g, 0.118mol)at 0°C over a period of 60 min. The reaction mixture was further stirred at 0°C for 1.5h and at10-15°C for 3h. To the reaction mixture was then added anhydrous K2CO3 (16.3g, 0.118mol) , andthis mixture stirred overnight. The oily layer was separated, added K2CO3 (1.63g, 0.012mol) andstirred for 15min and again decanted. The remaining residual material from the K2CO3 wasrecovered by washing all the solid K2CO3 with ether .Ether washings were mixed with thedecanted oily product and concentrated on the rotary evaporator to give crude product ofS2N-Benzyl Substituted Compound 1 21g, 90.8percent Yield.To a 300 mL round bottom flask was charged 57.2 g (698 mmol) of 30 weight percent formaldehyde, which was cooled to OPart B. Part B. Part B. Part B.

N-(Methoxymethyl)-N-(trimethylsilylmethyl)benzylamine is useful reagent in synthesizing N-benzyl substituted pyrrolidines by [3+2] cycloaddition to α,ßunsaturated esters.

Molecular Weight:237.41
Hydrogen Bond Acceptor Count:2
Rotatable Bond Count:6
Exact Mass:237.154890892
Monoisotopic Mass:237.154890892
Topological Polar Surface Area:12.5
Heavy Atom Count:16
Complexity:185
Covalently-Bonded Unit Count:1
Compound Is Canonicalized:Yes