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[ CAS No. 53215-95-5 ]

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CAS No. :53215-95-5 MDL No. :MFCD00012192
Formula : C11H19NSi Boiling Point : 231.9°C at 760 mmHg
Linear Structure Formula :- InChI Key :-
M.W :193.36 g/mol Pubchem ID :353458
Synonyms :

Safety of [ 53215-95-5 ]

Signal Word:Warning Class:N/A
Precautionary Statements:P261-P305+P351+P338 UN#:N/A
Hazard Statements:H315-H319-H335 Packing Group:N/A
GHS Pictogram:

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  • Upstream synthesis route of [ 53215-95-5 ]
  • Downstream synthetic route of [ 53215-95-5 ]

[ 53215-95-5 ] Synthesis Path-Upstream   1~17

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  • [ 292638-85-8 ]
  • [ 17012-21-4 ]
YieldReaction ConditionsOperation in experiment
10.4 g
Stage #1: With N,N,N',N'-tetramethylguanidine In tetrahydrofuran at 20℃; for 1.5 h;
Stage #2: With trifluoroacetic acid In tetrahydrofuran
Paraformaldehyde (1.72 g, 54.3 mmol) was charged in the reactor followed by 100 mL THF and Benzyl-trimethylsilanylmethyl-amine (5) (10 g, 51.7 mmol). 1,1,3,3-tetramethylguanidine (119 mg, 130 μ, 1.03 mmol) was added to the suspension. The reaction mixture was stirred at RT for 1.5 h during which a clear solution was obtained. This solution was added dropwise over 30 min to a mixture consisting of TFA (301 mg, 203 μ, 2.59 mmol) and methyl acrylate (4.95 g, 56.9 mmol). After completion of the reaction (IPC by GC or HPLC, ca 3-5 h), the reaction mixture was concentrated under reduced pressure. The oily residue was dissolved in 25 mL MTBE and was washed twice washed with 60 mL water (60.0 g, 60 mL), then with 30 mL half saturated NaHC03 aq and 25 mL half saturated NaClaq. The organic phase was dried over MgS04, filtered and concentrated under reduced pressure to give 10.4 g of product (21) (89percent yield).
Reference: [1] Chemistry Letters, 1996, # 9, p. 747 - 748
[2] Patent: WO2013/160273, 2013, A1, . Location in patent: Page/Page column 108
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  • [ 17012-21-4 ]
Reference: [1] Chemistry Letters, 1984, p. 1117 - 1120
[2] Chemical & Pharmaceutical Bulletin, 1985, vol. 33, # 7, p. 2762 - 2766
[3] Patent: US2015/45408, 2015, A1,
[4] Patent: CN104817549, 2017, B,
  • 3
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  • [ 5747-92-2 ]
Reference: [1] Chemistry Letters, 1984, p. 1117 - 1120
[2] Chemistry Letters, 1984, p. 1117 - 1120
  • 4
  • [ 4206-67-1 ]
  • [ 100-46-9 ]
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YieldReaction ConditionsOperation in experiment
89% With potassium carbonate In acetonitrile at 20℃; for 12 h; 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).
Reference: [1] Tetrahedron Letters, 2015, vol. 56, # 23, p. 3014 - 3018
[2] Organic and Biomolecular Chemistry, 2016, vol. 14, # 44, p. 10502 - 10510
[3] Tetrahedron Letters, 2017, vol. 58, # 10, p. 949 - 954
[4] Tetrahedron, 2017, vol. 73, # 44, p. 6249 - 6261
  • 5
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YieldReaction ConditionsOperation in experiment
93.3% at 20 - 120℃; for 24 h; 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). 1H NMR (300 MHz, CDCl3): δ 7.32 - 7.24 (m, 5H), 3.76 (s, 2H), 2.06 (s, 2H), 0.07 (s, 9H).
83% for 16 h; Heating / reflux EXAMPLE 2; 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 MgSO4. The filtrate is concentrated under vacuum to give 1.77 kg (83percent) of N-(trimethylsilylmethyl)benzylamine. The above amine (1.77 kg, 9.14 mol) is added to a mixture of 37percent formaldehyde (0.89 kg, 10.96 mol) and methanol (0.35 kg, 10.96 mol) at 0° C. over a period of 30 min. The reaction mixture is further stirred at 0° C. for 1 h and at 10° C. to 15° C. for 3 h. To the reaction mixture is then added anhydrous K2CO3 (1 kg) and stirred for 2 h. The oily layer is decanted onto 100 g of K2CO3 and stirred for 15 min and again decanted. The remaining residual material from the K2CO3 is recovered by washing all the solid K2CO3 with ether. Ether washings are mixed with the decanted oily product and concentrated on rotary evaporator to give 2.10 kg (82percent) of the desired product 3-4, deemed pure enough to be used in the next step.
82% at 85℃; for 16 h; Large scale dd 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.
76% for 5 h; Reflux 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.
21 g for 16 h; Reflux; Inert atmosphere 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.

Reference: [1] Tetrahedron, 1996, vol. 52, # 16, p. 5669 - 5682
[2] Patent: WO2014/24125, 2014, A1, . Location in patent: Page/Page column 24
[3] European Journal of Medicinal Chemistry, 2010, vol. 45, # 5, p. 1717 - 1723
[4] Bioorganic and Medicinal Chemistry Letters, 2009, vol. 19, # 21, p. 6038 - 6041
[5] Patent: US2006/128789, 2006, A1, . Location in patent: Page/Page column 7
[6] Organic Process Research and Development, 2005, vol. 9, # 2, p. 193 - 197
[7] Journal of Organic Chemistry, 2001, vol. 66, # 7, p. 2526 - 2529
[8] Journal of the American Chemical Society, 2011, vol. 133, # 26, p. 10184 - 10194
[9] Patent: CN104817549, 2017, B, . Location in patent: Paragraph 0027-0030
[10] Journal of the Chemical Society - Perkin Transactions 1, 1998, # 22, p. 3867 - 3872
[11] Tetrahedron Letters, 2014, vol. 55, # 8, p. 1491 - 1495
[12] Journal of Organic Chemistry, 1996, vol. 61, # 10, p. 3362 - 3374
[13] Tetrahedron, 1985, vol. 41, # 17, p. 3529 - 3535
[14] Journal of Organic Chemistry, 1985, vol. 50, # 21, p. 4006 - 4014
[15] Zeitschrift fuer Chemie (Stuttgart, Germany), 1974, vol. 14, # 7, p. 289 - 290
[16] Tetrahedron Letters, 1983, vol. 24, # 33, p. 3447 - 3450
[17] Tetrahedron, 1994, vol. 50, # 27, p. 8185 - 8194
[18] Synthesis, 2001, # 8, p. 1263 - 1267
[19] Patent: US4994486, 1991, A,
[20] Patent: US2006/63761, 2006, A1, . Location in patent: Page/Page column 6; 13
[21] Journal of Organic Chemistry, 2012, vol. 77, # 24, p. 11071 - 11078
[22] Patent: WO2014/39489, 2014, A1, . Location in patent: Page/Page column 86; 87
[23] Synlett, 2016, vol. 27, # 2, p. 282 - 286
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Reference: [1] Canadian Journal of Chemistry, 1977, vol. 55, p. 2589 - 2600
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Reference: [1] Journal of Organic Chemistry, 2016, vol. 81, # 6, p. 2340 - 2354
  • 8
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Reference: [1] Journal of the Chemical Society, Perkin Transactions 2: Physical Organic Chemistry (1972-1999), 1993, # 12, p. 2411 - 2414
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Reference: [1] Journal of the Chemical Society, Perkin Transactions 2: Physical Organic Chemistry (1972-1999), 1993, # 12, p. 2411 - 2414
  • 10
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Reference: [1] Journal of the Chemical Society, Perkin Transactions 2: Physical Organic Chemistry (1972-1999), 1993, # 12, p. 2411 - 2414
  • 11
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Reference: [1] Journal of the Chemical Society, Perkin Transactions 2: Physical Organic Chemistry (1972-1999), 1993, # 12, p. 2411 - 2414
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  • [ 93102-05-7 ]
YieldReaction ConditionsOperation in experiment
97.5%
Stage #1: at 0℃;
Stage #2: With potassium carbonate In water at 20℃; for 2 h;
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). 1H NMR (300 MHz, CDCl3): δ 7.35 - 7.18 (m, 5H), 3.99 (s, 2H), 3.75 (s, 2H), 3.22 (s, 3H), 2.18 (s, 2H), 0.13 (s, 9H).
Reference: [1] Patent: WO2014/24125, 2014, A1, . Location in patent: Page/Page column 24-25
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YieldReaction ConditionsOperation in experiment
91%
Stage #1: at 0 - 15℃; for 4 h; Large scale
Stage #2: at 20℃; Large scale
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 91percent
82% With potassium carbonate In methanol at 0 - 15℃; for 5.75 h; EXAMPLE 2; 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 MgSO4. The filtrate is concentrated under vacuum to give 1.77 kg (83percent) of N-(trimethylsilylmethyl)benzylamine. The above amine (1.77 kg, 9.14 mol) is added to a mixture of 37percent formaldehyde (0.89 kg, 10.96 mol) and methanol (0.35 kg, 10.96 mol) at 0° C. over a period of 30 min. The reaction mixture is further stirred at 0° C. for 1 h and at 10° C. to 15° C. for 3 h. To the reaction mixture is then added anhydrous K2CO3 (1 kg) and stirred for 2 h. The oily layer is decanted onto 100 g of K2CO3 and stirred for 15 min and again decanted. The remaining residual material from the K2CO3 is recovered by washing all the solid K2CO3 with ether. Ether washings are mixed with the decanted oily product and concentrated on rotary evaporator to give 2.10 kg (82percent) of the desired product 3-4, deemed pure enough to be used in the next step.
64% at 0 - 25℃; for 4 h; To 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.
43.8% at 0 - 20℃; for 1.83333 h; Synthesis of benzyl(methoxymethyl)trimethylsilanylmethylamine (Reaction with 1.3 eq. of Paraformaldehyde)
2.00 g (0.014 mol) of potassium carbonate, 24.4 g (0.76 mol) of methanol and 15.6 g (0.52 mol) of paraformaldehyde are initially charged and cooled to 0° C.
At this temperature, within 30 min, 77.4 g (0.40 mol) of benzyltrimethylsilanylmethylamine are metered in.
The biphasic reaction mixture is stirred at 0° C. for a further 1 h and then warmed to room temperature within 20 min.
Within 1 min, 190.9 g of pentane are metered in.
The biphasic reaction mixture is separated and the upper organic phase is dried azeotropically for 2 h.
The organic phase is concentrated and then fractionally distilled.
Yield 74.9 g (79percent) of a colorless liquid.
DSC analyses: upper layer of the biphasic reaction mixture after the further reaction time (onset temperature: 154° C., decomposition enthalpy 414 J/g) lower layer of the biphasic reaction mixture after the further reaction time (onset temperature: 72° C., decomposition enthalpy 123 J/g) distillation bottoms (onset temperature: 134° C., decomposition enthalpy 461 J/g).
Example 4
Synthesis of benzyl(methoxymethyl)trimethylsilanylmethylamine (Equimolar Reaction)2.50 g (0.018 mol) of potassium carbonate, 30.4 g (0.95 mol) of methanol and 15.0 g (0.50 mol) of paraformaldehyde are initially charged and cooled to 0° C. At this temperature, within 30 min, 96.7 g (0.50 mol) of benzyltrimethylsilanylmethylamine are metered in. The biphasic reaction mixture is stirred at 0° C. for a further 1 h and then warmed to room temperature within 20 min. Within 1 min, 190.9 g of pentane are metered in. The biphasic reaction mixture is separated and the upper, organic phase is dried azeotropically for 2 h. The organic phase is concentrated and then fractionally distilled. Yield 105.9 g (89percent) of a colorless liquid. -b.p. 94° C./1 mbar. -1H NMR(C6D6): δ=0.09 (s, 9H), 2.21 (s, 2H), 3.00 (s, 3H), 3.75 (s, 2H), 3.87 (s, 2H), 7.10-7.45 (m, 5H).DSC analyses: upper layer of the biphasic reaction mixture after the further reaction time (onset temperature: 225° C., decomposition enthalpy 163 J/g) lower layer of the biphasic reaction mixture after the further reaction time (onset temperature: 80° C., decomposition enthalpy 14 J/g) distillation bottoms (onset temperature: 210° C., decomposition enthalpy 646 J/g).
Example 5Synthesis of benzyl(methoxymethyl)trimethylsilanylmethylamine (Reactions with Different StoichiometriesThe reactions were carried out analogously to Example 4, with the stoichiometries set forth in Table 1. In the inventive process, the stoichiometry is crucial for yield and onset temperature. The decomposition enthalpies reported are based on the distillation bottoms. TABLE 1 Decompo- Decompo- eq. sition sition Experiment Yield PFA Onset 1 enthalpy 1 Onset 2 enthalpy 2 4(a) 43.8 0.90 260° C. 69 J/g 4(b) 66.0 0.95 256° C. 400 J/g 4(c) 81.3 1.00 245° C. 91 J/g - - 4(d) 81.2 1.05 158° C. 291 J/g 361° C. 12 J/g In the case of substoichiometric use of paraformaldehyde, the yield falls (from 81.3percent at 1.0 equivalent to 43.8percent at 0.90 equivalent). In the case of superstoichiometric use of paraformaldehyde (1.05 eq.), the yield remains virtually unchanged, but the onset temperature falls from approx. 250° C. to 158° C.
1.21 g at 0 - 15℃; for 5.5 h; Inert atmosphere 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.

Reference: [1] Bioorganic and Medicinal Chemistry Letters, 2009, vol. 19, # 21, p. 6038 - 6041
[2] Patent: CN104817549, 2017, B, . Location in patent: Paragraph 0032-0034
[3] Journal of Organic Chemistry, 2016, vol. 81, # 6, p. 2340 - 2354
[4] Patent: US2006/128789, 2006, A1, . Location in patent: Page/Page column 7
[5] Chemistry Letters, 1984, p. 1117 - 1120
[6] European Journal of Medicinal Chemistry, 2010, vol. 45, # 5, p. 1717 - 1723
[7] Tetrahedron Letters, 2014, vol. 55, # 8, p. 1491 - 1495
[8] Journal of the Chemical Society - Perkin Transactions 1, 1998, # 22, p. 3867 - 3872
[9] Patent: US2009/36700, 2009, A1, . Location in patent: Page/Page column 3-4; 4
[10] Journal of Organic Chemistry, 1987, vol. 52, # 2, p. 235 - 244
[11] Journal of Organic Chemistry, 1996, vol. 61, # 10, p. 3362 - 3374
[12] Patent: US2006/63761, 2006, A1, . Location in patent: Page/Page column 6; 13
[13] Journal of the American Chemical Society, 2011, vol. 133, # 26, p. 10184 - 10194
[14] Organic Process Research and Development, 2005, vol. 9, # 2, p. 193 - 197
[15] Patent: WO2013/160273, 2013, A1, . Location in patent: Page/Page column 91
[16] Patent: WO2014/39489, 2014, A1, . Location in patent: Page/Page column 87
[17] Patent: US2015/45408, 2015, A1, . Location in patent: Paragraph 0434-0435
[18] Synlett, 2016, vol. 27, # 2, p. 282 - 286
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YieldReaction ConditionsOperation in experiment
69%
Stage #1: at 0℃; for 0.166667 h;
Stage #2: at 20℃; for 73 h;
To a 300 mL round bottom flask was charged 57.2 g (698 mmol) of 30 weight percent formaldehyde, which was cooled to O0C. To the cold formaldehyde was added 89.92 g (485 mmol) of Benzyl-methoxymethyl-trimethylsilanylmethyl-amine. After 10 min, 60 mL of methanol were added drop-wise, followed by excessive potassium carbonate (105 g). The reaction mixture was stirred for 1 hour then the liquid phase was separated. More potassium carbonate was added to the liquid phase (20 g) and the reaction mixture was allowed to stir at room temperature for 72 hours. The reaction mixture was filtered and the excess methanol evaporated. The liquid was purified by vacuum distillation to yield 51.3 g (216 mmol) of clear liquid, 69percent. Mass spectrum (APCl) m/e 238 p+1. 1H NMR (CDCI3, 400 MHz)_7.34-7.30(m, 5H), 4.01 (s, 2H), 3.77(s, 2H), 3.19(s, 3H), 2.19(s, 2H), 0.054(s, 9H) ppm.
Reference: [1] Patent: WO2006/61711, 2006, A1, . Location in patent: Page/Page column 17
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YieldReaction ConditionsOperation in experiment
92% With formaldehyd; potassium carbonate In methanol Part B.
Preparation of N-benzyl-N-(trimethylsilylmethyl)aminomethyl methyl ether.
To a stirred mixture of methanol (1.25 mL, 31 mmol) and 37percent aqueous formaldehyde (2.56 mL, 31 mmol) at 0° C. was added N-benzyl-N-(trimethylsilylmethyl)amine (5.0 g, 26 mmol) dropwise over 5 minutes.
The resulting mixture was stirred for 2 h.
Anhydrous potassium carbonate (1.02 g, 7.4 mmol) was added and the mixture was stirred at 0° C. for 30 min.
The reaction mixture was diluted with water and extracted twice with ether.
The combined organic extracts were washed with brine, dried over sodium sulfate and concentrated in vacuo to afford 5.6 g (92percent) of the title compound. 1 H NMR (CDCl3): δ 7.30-7.15 (m, 5H), 3.95 (s, 2H), 3.71 (s, 2H), 3.19 (s, 3H), 2.14 (s, 2H).
92% With formaldehyd; potassium carbonate In methanol Part B.
Preparation of N-benzyl-N-(trimethylsilylmethyl)aminomethyl methyl ether.
To a stirred mixture of methanol (1.25 mL, 31 mmol) and 37percent aqueous formaldehyde (2.56 mL, 31 mmol) at 0° C. was added N-benzyl-N-(trimethylsilylmethyl)amine (5.0 g, 26 mmol) dropwise over 5 minutes.
The resulting mixture was stirred for 2 h.
Anhydrous potassium carbonate (1.02 g, 7.4 mmol) was added and the mixture was stirred at 0° C. for 30 min.
The reaction mixture was diluted with water and extracted twice with ether.
The combined organic extracts were washed with brine, dried over sodium sulfate and concentrated in vacuo to afford 5.6 g (92percent) of the title compound. 1 H NMR (CDCl3): δ 7.30-7.15 (m, 5H), 3.95 (s, 2H), 3.71 (s, 2H), 3.19 (s, 3H), 2.14 (s, 2H).
92% With formaldehyd; potassium carbonate In methanol Part B.
Preparation of N-benzyl-N-(trimethylsilylmethyl)aminomethyl methyl ether.
To a stirred mixture of methanol (1.25 mL, 31 mmol) and 37percent aqueous formaldehyde (2.56 mL, 31 mmol) at 0° C was added N-benzyl-N-(trimethylsilylmethyl)amine (5.0 g, 26 mmol) dropwise over 5 minutes.
The resulting mixture was stirred for 2 h.
Anhydrous potassium carbonate (1.02 g, 7.4 mmol) was added and the mixture was stirred at 0° C for 30 min.
The reaction mixture was diluted with water and extracted twice with ether.
The combined organic extracts were washed with brine, dried over sodium sulfate and concentrated in vacuo to afford 5.6 g (92percent) of the title compound. 1H NMR (CDCl3): δ 7.30-7.15 (m, 5H), 3.95 (s, 2H), 3.71 (s, 2H), 3.19 (s, 3H), 2.14 (s, 2H).
92% With formaldehyd; potassium carbonate In methanol Part B.
Preparation of N-benzyl-N-(trimethylsilylmethyl)aminomethyl methyl ether.
To a stirred mixture of methanol (1.25 mL, 31 mmol) and 37percent aqueous formaldehyde (2.56 mL, 31 mmol) at 0° C was added N-benzyl-N-(trimethylsilylmethyl)amine (5.0 g, 26 mmol) dropwise over 5 minutes.
The resulting mixture was stirred for 2 h.
Anhydrous potassium carbonate (1.02 g, 7.4 mmol) was added and the mixture was stirred at 0° C for 30 min.
The reaction mixture was diluted with water and extracted twice with ether.
The combined organic extracts were washed with brine, dried over sodium sulfate and concentrated in vacuo to afford 5.6 g (92percent) of the title compound. 1H NMR (CDCl3): δ 7.30-7.15 (m, 5H), 3.95 (s, 2H), 3.71 (s, 2H), 3.19 (s, 3H), 2.14 (s, 2H).

Reference: [1] Patent: US6057342, 2000, A,
[2] Patent: US6057342, 2000, A,
[3] Patent: EP934265, 2003, B1,
[4] Patent: EP934265, 2003, B1,
  • 16
  • [ 53215-95-5 ]
  • [ 107-30-2 ]
  • [ 93102-05-7 ]
Reference: [1] Chemical & Pharmaceutical Bulletin, 1985, vol. 33, # 7, p. 2762 - 2766
  • 17
  • [ 109-72-8 ]
  • [ 53215-95-5 ]
  • [ 107-30-2 ]
  • [ 93102-05-7 ]
Reference: [1] Patent: US6245801, 2001, B1,
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