N-[(Trimethylsilyl)methyl]benzylamine

Colorless liquid

General procedure: Individual solutions of benzylamine derivatives (24.3 mmol of 37 (2.6 g), 28.0 mmol of 38 (3.4 g), 28.0 mmol of 39 (3.8 g), 11.2 mmol of 40 (1.4 g), 11.2 mmol of 41(2.0 g)) in acetonitrile (120 mL) containing K2CO3 (5.2 g (37.4 mmol) for 37, 6.5 g ( 46.7 mmol) for38-39, and 2.6 g (18.7 mmol) for 40-41) and Me3SiCH2I (4.0 g (18.7 mmol) for 37, 5.0 g (23.4 mmol) for 38-39, and 2.0 g (9.3 mmol) for 40-41) were stirred for 12 h at room temperature and concentrated in vacuo to give residues which were triturated with CH2Cl2. The triturates were dried and concentrated in vacuo to afford residues, which were subjected to silica gel column chromatography (EtOAc: hexane = 1: 8 ~ 1: 15) to yield 421 (3.2 g, 89percent), 43 (3.85 g, 79percent), 442 (3.3g, 63percent), 45 (1.51 g, 76 percent), and 46 (1.9 g, 78 percent).The mixture of benzylamine (59.516 g, 549.84 mmol) and (chloromethyl)- trimethylsilane (23.410 g, 187.02 mmol) was heated at 120°C for 4 hours, and then stirred at room temperature for 20 hours. To the mixture 78.328 g of potassium carbonate in 200 ml of water were added and the whole was extracted with diethyl ether (2 x 30 ml). Organic layer was dried over sodium sulphate. Solvent and drying agent were removed to obtain colorless liquid. The excess of benzylamine was distilled off (38-45°C/0.36 mm Hg) using Vigreux column. 35.500 g of the title product in the form of a colorless liquid were obtained (yield 93.3percent). N-(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 MgSOdd in 2L multi-mouth bottle1000.0g (8.2mo 1)Chloromethyltrimethylsilane, 1746 · 0g (16.3mo 1) benzylamine and 1 L of acetonitrile, The reaction was refluxed at 85 ° C for 16 h, Recovered to room temperature, filtered, the filtrate was concentrated under reduced pressure, The residue was added to 10 L of distilled water, The aqueous phase was extracted three times with 5 L of n-hexane, the organic phases were combined, The organic phase was concentrated to give 1282.0 g of benzyl as a yellow oilTrimethylsilylmethylamine in 82percent yield.A mixture containing 34.8 mL of benzylamine (ii) (34.2 g, 318.6 mmol)and 15.2 mL (chloromethyl)trimethylsilane (i) (13.4 g, 109 mmol) was refluxed for 5h.After this period, distilled water (100 mL) was added and the extraction was carried outwith hexane (3x100 mL). The organic phase was dried over anhydrous Na2SO4, filteredand the solvent removed under reduced pressure. The residue was distilled under highvacuum collecting the compound iii in a temperature range of 114-115 ° C as a colorlessliquid in 76percent yield (15.9 g, 82.3 mmol).1H NMR (CDCl3, 400.15 MHz) δ (ppm): 0.04 (br.s, 9H), 1.19 (br.s, 1H), 2.05 (s, 2H), 3.79 (s, 2H ), 7.22-7.35 (m, 5H).13C NMR (CDCl3, 100.4 MHz) δ (ppm): -2.60, 39.5, 58.01, 126.8, 128.1, 128.3, 140.6.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.

Molecular Weight:193.36
Hydrogen Bond Donor Count:1
Hydrogen Bond Acceptor Count:1
Rotatable Bond Count:4
Exact Mass:193.128676145
Monoisotopic Mass:193.128676145
Topological Polar Surface Area:12
Heavy Atom Count:13
Complexity:134
Covalently-Bonded Unit Count:1
Compound Is Canonicalized:Yes