66389-80-8|tert-Butyl 4-cyanobenzylcarbamate| Ambeed

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Quality Control of [ 66389-80-8 ] Purity: 97% SDS Specification

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Product Details of [ 66389-80-8 ]

CAS No. :	66389-80-8
Formula :	C₁₃H₁₆N₂O₂
M.W :	232.28
SMILES Code :	O=C(OC(C)(C)C)NCC1=CC=C(C#N)C=C1
MDL No. :	MFCD08436197
InChI Key :	NCGBJBDHEYDWEC-UHFFFAOYSA-N
Pubchem ID :	10799583

Safety of [ 66389-80-8 ]

GHS Pictogram:
Signal Word:	Warning
Hazard Statements:	H302
Precautionary Statements:	P280-P305+P351+P338

Application In Synthesis of [ 66389-80-8 ]

* All experimental methods are cited from the reference, please refer to the original source for details. We do not guarantee the accuracy of the content in the reference.

Downstream synthetic route of [ 66389-80-8 ]

[ 66389-80-8 ] Synthesis Path-Downstream 1~35

1
[ 66389-78-4 ]
[ 66389-80-8 ]

References: [1]Journal of the Chemical Society. Chemical communications,1977,p. 758 - 759.

2
[ 66389-77-3 ]
[ 17201-43-3 ]
[ 66389-80-8 ]

References: [1]Journal of the Chemical Society. Perkin transactions I,1978,p. 1088 - 1090.

3
[ 66389-80-8 ]
[ 217313-80-9 ]

References: [1]Synthetic Communications,1998,vol. 28,p. 4419 - 4429.

4
[ 172348-74-2 ]
[ 66389-80-8 ]

References: [1]Synthetic Communications,1998,vol. 28,p. 4419 - 4429.

5
[ 24424-99-5 ]
[ 10406-25-4 ]
[ 66389-80-8 ]

Yield	Reaction Conditions	Operation in experiment
93%	With triethylamine; In dichloromethane; at 20℃;	To a round-bottom flask equipped with a stir bar was added 17a-b (1.0 eq), Boc2O (1.1 eq), CH2Cl2 (10mL/mmol), and triethylamine (1.5 eq). The reaction mixture was stirred at room temperature overnight. The reaction was concentrated in vacuo and partitioned between ethyl ether and 1M HCl. The organic layer were separated, washed with saturated NaHCO3 and brine, dried over MgSO4, and concentrated in vacuo to give a white crystalline solid. 4.2.4.2 128 tert-Butyl (4-cyanobenzyl)carbamate (18a) Yield: 93%. MP: 114-116C. 1H NMR (400MHz, CDCl3) delta 7.62 (d, J=7.9Hz, 2H, -ArH), 7.39 (d, J=8.5Hz, 2H, -ArH), 4.96 (s, 1H, -NH-), 4.37 (d, J=5.9Hz, 2H, -CH2-), 1.46 (s, 9H, -CH3)
93%	With triethylamine; In dichloromethane; at 20℃;	General procedure: To a round-bottom flask equipped with a stir bar was added 27a-b (1.0 eq), Boc2O (1.1 eq), CH2Cl2 (10 mL/mmol), and triethylamine (1.5 eq). The reaction mixture was stirred at room temperature overnight. The reaction was concentrated in vacuo and partitioned between ethyl ether and 1 M HCl. The organic layer were separated, washed with saturated NaHCO3, brine, dried over MgSO4, and concentrated in vacuo to give a white crystalline solid. Example 86 Synthesis of 210 tert-Butyl (4-cyanobenzyl) carbamate (28a) (0243) The synthesis follows the general procedure described in Example 85. Yield: 93%. MP: 114-116 C. 1H NMR (400 MHz, CDCl3) delta 7.62 (d, J=7.9 Hz, 2H, -ArH), 7.39 (d, J=8.5 Hz, 2H, -ArH), 4.96 (s, 1H, -NH-), 4.37 (d, J=5.9 Hz, 2H, -CH2-), 1.46 (s, 9H, -CH3).

References: [1]Journal of Medicinal Chemistry,2013,vol. 56,p. 1843 - 1852.
[2]European Journal of Medicinal Chemistry,2018,vol. 150,p. 796 - 808.
[3]Patent: US2019/2450,2019,A1 .Location in patent: Paragraph 0242-0243.
[4]Bioorganic and medicinal chemistry letters,2002,vol. 12,p. 644 - 648.
[5]Bioorganic and Medicinal Chemistry Letters,2003,vol. 13,p. 3477 - 3482.
[6]Patent: WO2013/138665,2013,A1 .Location in patent: Paragraph 00095.
[7]Journal of Medicinal Chemistry,2014,vol. 57,p. 98 - 109.
[8]Journal of the American Chemical Society,2020,vol. 142,p. 1057 - 1064.

6
[ 66389-80-8 ]
[ 220648-78-2 ]

Yield	Reaction Conditions	Operation in experiment
99%	With hydroxylamine hydrochloride; triethylamine; In tetrahydrofuran; at 75℃; for 15h;	(2) To a solution of hydroxylamine hydrochloride (2.24 g, 32.3 mmol) in dimethyl sulfoxide (10.6 mL), triethylamine (4.51 mL, 32.4 mmol) was added and the resulting mixture was stirred at room temperature for an hour. The precipitating salt was filtered and washed with THF. The THF was distilled off under reduced pressure and after adding the foregoing compound (n-2) (1.50 g, 6.46 mmol), the resulting mixture was stirred at 75 C. for 15 hours. The reaction mixture was cooled to room temperature and after adding water, extraction was conducted with ethyl acetate. The organic layer was successively washed with water and saturated brine and dried over anhydrous sodium sulfate. The solvents were distilled off under reduced pressure to give tert-butyl 4-(N?-hydroxycarbamimidoyl)benzylcarbamate (n-3) (amount, 1.70 g; yield, 99%).
99%	With hydroxylamine hydrochloride; triethylamine; In dimethyl sulfoxide; at 75℃; for 16h;	To a solution of hydroxylamine hydrochloride (2.24 g, 32.3 mmol) in dimethyl sulfoxide (10.6 mL), triethylamine (4.51 mL, 32.4 mmol) was added and the resulting mixture was stirred at room temperature for an hour. The precipitating salt was filtered and washed with THF. The THF was distilled off under reduced pressure and after adding the foregoing compound (n-2) (1.50 g, 6.46 mmol), the resulting mixture was stirred at 75C for 15 hours. The reaction mixture was cooled to room temperature and after adding water, extraction was conducted with ethyl acetate. The organic layer was successively washed with water and saturated brine and dried over anhydrous sodium sulfate. The solvents were distilled off under reduced pressure to give tert-butyl 4-(N'-hydroxycarbamimidoyl)benzylcarbamate (n-3) (amount, 1.70 g; yield, 99%).
	With hydroxylamine hydrochloride; N-ethyl-N,N-diisopropylamine; In methanol;Heating / reflux;	130 g (0.56 mol) of product 3a, 58.4 g (0.84 mol) of hydroxylamine×HCl and 146 ml of DIEA were dissolved in 1.5 l of methanol. The mixture was boiled under reflux for 6 h and then stirred at room temperature overnight. The solvent was removed in vacuo, and the oily residue was dissolved in 1.5 l of acetic acid, mixed with 160 ml (1.68 mol) of acetic anhydride and stirred for 30 min. The solvent was removed in vacuo, and the residue was taken up with ethyl acetate and washed 3× with NaCl-saturated water and then dried over Na2SO4. The solvent was removed as far as possible in vacuo, and the product was crystallized from ethyl acetate. Yield: 110.6 g (0.36 mol) of crystalline solid, HPLC: 39.76% B

References: [1]Patent: US2016/130232,2016,A1 .Location in patent: Paragraph 0297.
[2]Patent: KR2016/18745,2016,A .Location in patent: Paragraph 0463; 0465.
[3]Journal of Medicinal Chemistry,2014,vol. 57,p. 98 - 109.
[4]Angewandte Chemie - International Edition,2012,vol. 51,p. 11463 - 11467.
[5]Bioorganic and medicinal chemistry letters,2002,vol. 12,p. 644 - 648.
[6]Patent: US2007/66539,2007,A1 .Location in patent: Page/Page column 8.
[7]Patent: WO2013/138665,2013,A1 .Location in patent: Paragraph 00095.

7
[ 66389-80-8 ]
[ 108468-00-4 ]

References: [1]Journal of Medicinal Chemistry,2013,vol. 56,p. 1843 - 1852.
[2]Bioorganic and Medicinal Chemistry Letters,2003,vol. 13,p. 3477 - 3482.

8
[ 24424-99-5 ]
4‐(2‐aminoethyl)benzonitrile hydrochloride [ No CAS ]
[ 66389-80-8 ]

Yield	Reaction Conditions	Operation in experiment
	With sodium hydroxide; In 1,4-dioxane; at 20℃; for 16h;	b) N-Boc-4-aminomethylbenzonitrile; To a solution of 4-aminoethylbenzonitrile hydrochloride (15g, 94mmol) in dioxane/1 N NaOH 1/1 (450ml) is added BoC2O (28.8g, 132mmol). The reaction mixture is stirred at room temperature under inert atmosphere for 16 hours. The precipitate is collected and dried to yield N-boc-4-aminomethylbenzonithle without further purification, m/z = 233.3 (M+H)+

References: [1]Patent: WO2008/37476,2008,A1 .Location in patent: Page/Page column 12.

9
[ 66389-80-8 ]
[ 1456610-74-4 ]

Yield	Reaction Conditions	Operation in experiment
	With hydroxylamine; In tetrahydrofuran; water; at 5 - 20℃; for 16h;	c) N-Boc-4-aminomethyl-N-hydroxy-benzamidine; To a solution of N-Boc-4-aminoethylbenzonitrile (14g; 60mmol) in THF (500ml) is added at 50C a solution of hydroxy Ia mine in water (1/1 ; 80ml; 1.8 mol). The reaction mixture is then stirred at room temperature for 16 hours. The reaction mixture is diluted with water and THF is removed under vacuo. The resulting precipitate is collected by filtration and dried. Pure title compound is obtained by recrystallization from diethylether.
	With hydroxylamine hydrochloride; N-ethyl-N,N-diisopropylamine; In ethanol; at 90℃; for 4h;	tert-Butyl 4-(5-(trifluoromethyl)-1 ,2,4-oxadiazol-3-yl)benzylcarbamate: To a suspension of ferf-butyl 4-cyanobenzylcarbamate (1.32 g, 5.70 mmol), i'-Pr2NEt (2.99 mL, 17.10 mmol) in ethanol (26 mL) was added hydroxylamine hydrochloride (380 mg, 1 1.4 mmol). The reaction mixture was stirred at 90 C for 4 h. The solvents were removed under reduced pressure, and the residue was dissolved in THF (26.0 mL

References: [1]Patent: WO2008/37476,2008,A1 .Location in patent: Page/Page column 12-13.
[2]Patent: WO2013/66839,2013,A2 .Location in patent: Page/Page column 31.

10
[ 66389-80-8 ]
N-(4-aminomethyl-benzyl)-2-(6-methyl-2-oxo-3-phenylmethanesulfonylamino-2H-pyridin-1-yl)-acetamide [ No CAS ]

References: [1]Bioorganic and Medicinal Chemistry Letters,2003,vol. 13,p. 3477 - 3482.

11
[ 66389-80-8 ]
(4-[2-(6-methyl-2-oxo-3-phenylmethanesulfonylamino-2H-pyridin-1-yl)-acetylamino]-methyl}-benzyl)-carbamic acid tert-butyl ester [ No CAS ]

References: [1]Bioorganic and Medicinal Chemistry Letters,2003,vol. 13,p. 3477 - 3482.

12
[ 84466-87-5 ]
[ 66389-80-8 ]

References: [1]Bioorganic and Medicinal Chemistry Letters,2003,vol. 13,p. 3477 - 3482.

13
[ 17201-43-3 ]
[ 66389-80-8 ]

References: [1]Bioorganic and Medicinal Chemistry Letters,2003,vol. 13,p. 3477 - 3482.
[2]Synthetic Communications,1998,vol. 28,p. 4419 - 4429.
[3]Journal of the Chemical Society. Chemical communications,1977,p. 758 - 759.

14
[ 66389-80-8 ]
[ 600707-97-9 ]

References: [1]Bioorganic and medicinal chemistry letters,2002,vol. 12,p. 644 - 648.

15
[ 66389-80-8 ]
[ 380237-42-3 ]

References: [1]Bioorganic and medicinal chemistry letters,2002,vol. 12,p. 644 - 648.

16
[ 66389-80-8 ]
[ 380237-44-5 ]

References: [1]Bioorganic and medicinal chemistry letters,2002,vol. 12,p. 644 - 648.

17
[ 66389-80-8 ]
C₁₂H₁₆N₄O₃*ClH [ No CAS ]

References: [1]Bioorganic and medicinal chemistry letters,2002,vol. 12,p. 644 - 648.

18
[ 66389-80-8 ]
benzylsulfonyl-D-Ser-Gly-4-Amba [ No CAS ]

References: [1]Bioorganic and medicinal chemistry letters,2002,vol. 12,p. 644 - 648.

19
[ 66389-80-8 ]
C₂₉H₃₃N₅O₇S [ No CAS ]

References: [1]Bioorganic and medicinal chemistry letters,2002,vol. 12,p. 644 - 648.

20
[ 51779-32-9 ]
[ 66389-80-8 ]

References: [1]Synthetic Communications,1998,vol. 28,p. 4419 - 4429.

21
[ 66389-80-8 ]
[ 162696-15-3 ]

References: [1]Synthetic Communications,1998,vol. 28,p. 4419 - 4429.
[2]Angewandte Chemie - International Edition,2017,vol. 56,p. 3718 - 3722.
Angew. Chem.,2017,vol. 129,p. 3772 - 3776,5.

22
[ 66389-80-8 ]
[ 217313-81-0 ]

References: [1]Synthetic Communications,1998,vol. 28,p. 4419 - 4429.

23
[ 66389-80-8 ]
[ 162696-14-2 ]

References: [1]Synthetic Communications,1998,vol. 28,p. 4419 - 4429.

24
[ 66389-80-8 ]
melagatran [ No CAS ]

References: [1]Synthetic Communications,1998,vol. 28,p. 4419 - 4429.

25
[ 66389-80-8 ]
[ 172348-75-3 ]

References: [1]Synthetic Communications,1998,vol. 28,p. 4419 - 4429.

26
[ 66389-77-3 ]
[ 66389-80-8 ]

References: [1]Journal of the Chemical Society. Chemical communications,1977,p. 758 - 759.

27
[ 24424-99-5 ]
[ 66389-80-8 ]

Yield	Reaction Conditions	Operation in experiment
97%		4-Cyanobenzylamine hydrochloride salt (CBA HCl) (200 g, 1.19 mol) was dissolved in 1.25 L of distilled deionised water (6.25 volumes) in a 5 L reactor with a mantle temperature of 25 0C. At 25 0C, the solution was clear within 15 minutes. To the clear solution was added a solution of 52 g (1.1 eq.) of NaOH in 400 mL of water. The solution was added at a rate of 10-15 mL/min. A small temperature increase (~3 C) was noted. A large amount of precipitate (the free amine) appeared during the addition. After the addition, the pH of the mixture was >12.A solution of BoC2O (285 g, 1.30 mol, 1.1 eq.) in MeOH (200 mL) was added drop- wise to the white suspension at an average rate of ~10 mL/min. Carbon dioxide evolution and a small temperature increase (5 C over 30 min) was noted during the addition. As the addition continued, the consistency of the slurry/suspension changed as the insoluble amine was converted to the insoluble Boc-protected amine. EPO <DP n="17"/>The reaction was followed by taking samples of the supernatant in the reactor and comparing the peak area of the starting material with a calibration curve of the starting material (HPLC column: Symmetry Shield RP8, 3.5 mum, 50 mm; 205 and 230 nm - see Example 3 for more details). A 98% conversion was obtained 6 hours after the addition of Boc2O was complete. The reaction was left overnight to obtain a 99% conversion. The slurry was filtered and the solid washed with 2 x 500 mL water. The material was dried under vacuum at 40 C to give Boc-CBA (265g, 97% yield, 98.7% purity (HPLC by analogy to Example 3, no Boc2O detected) .

References: [1]Patent: WO2006/90153,2006,A1 .Location in patent: Page/Page column 15-16.
[2]Organic Letters,2011,vol. 13,p. 3956 - 3959.
[3]Journal of the American Chemical Society,2012,vol. 134,p. 4465 - 4468.

28
[ 51779-32-9 ]
[ 17201-43-3 ]
[ 66389-80-8 ]

Yield	Reaction Conditions	Operation in experiment
18.5 g (94%)	With sodium hydroxide; In tetrahydrofuran; methanol; water;	B) Preparation of N-Boc-p-(aminomethyl)benzonitrile. To a stirring suspension of sodium hydride (4.6 g, 115 mmol, 60% dispersion in oil) in tetrahydrofuran (150 mL) was added 4-(bromomethyl)benzonitrile (20.5 g, 105 mmol). To this mixture was added (slowly via an addition funnel) a solution of di-t-butyl iminodicarboxylate (25 g, 115 mmol). After stirring for 16 hours, the mixture was diluted with diethyl ether (500 mL) and washed twice with water (250 mL). The organic phase was then dried (MgSO4), filtered and concentrated to give 40.2 g of crude solid. The resulting solid (28.3 g, 85 mmol) was then dissolved in tetrahydrofuran (150 mL) and a solution of sodium hydroxide (3.4 g, 85 mmol) in methanol (300 mL) was added. After stirring overnight, the solution was concentrated to about one-half volume and water was added to promote precipitation of the product. The precipitate was filtered and dried in vacuo to give 18.5 g (94%) of a white solid.
18.5 g (94%)	With sodium hydroxide; In tetrahydrofuran; methanol; water;	B) Preparation of N-Boc-p-(aminomethyl)benzonitrile To a stirring suspension of sodium hydride (4.6 g, 115 mmol, 60% dispersion in oil) in tetrahydrofuran (150 mL) was added 4-(bromomethyl)benzonitrile (20.5 g, 105 mmol). To this mixture was added (slowly via an addition funnel) a solution of di-t-butyl iminodicarboxylate (25 g, 115 mmol). After stirring for 16 hours, the mixture was diluted with diethyl ether (500 mL) and washed twice with water (250 mL). The organic phase was then dried (MgSO4), filtered and concentrated to give 40.2 g of crude solid. The resulting solid (28.3 g, 85 mmol) was then dissolved in tetrahydrofuran (150 mL) and a solution of sodium hydroxide (3.4 g, 85 mmol) in methanol (300 mL) was added. After stirring overnight, the solution was concentrated to about one-half volume and water was added to promote precipitation of the product. The precipitate was filtered and dried in vacuo to give 18.5 g (94%) of a white solid.
18.5 g (94%)	With sodium hydroxide; In tetrahydrofuran; methanol; water;	B) Preparation of N-Boc-p-(aminomethyl)benzonitrile To a stirring suspension of sodium hydride (4.6 g, 115 mmol, 60% dispersion in oil) in tetrahydrofuran (150 mL) was added 4-(bromomethyl)benzonitrile (20.5 g, 105 mmol). To this mixture was added (slowly via an addition funnel) a solution of di-t-butyl iminodicarboxylate (25 g, 115 mmol). After stirring for 16 hours, the mixture was diluted with diethyl ether (500 mL) and washed twice with water (250 mL). The organic phase was then dried (MgSO4), filtered and concentrated to give 40.2 g of crude solid. The resulting solid (28.3 g, 85 mmol) was then dissolved in tetrahydrofuran (150 mL) and a solution of sodium hydroxide (3.4 g, 85 mmol) in methanol (300 mL) was added. After stirring overnight, the solution was concentrated to about one-half volume and water was added to promote precipitation of the product. The precipitate was filtered and dried in vacuo to give 18.5 g (94%) of a white solid.

References: [1]Patent: US5705487,1998,A .
[2]Patent: US5710130,1998,A .
[3]Patent: US5726159,1998,A .

29
[ 66389-80-8 ]
[ 593-56-6 ]
Boc-Pab(OMe) [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
	With mercaptoacetic acid; triethylamine; In ethanol; water; at 55 - 90℃;	Methoxyamidination of Boc-CBA (to give Boc-Pab(OMe) A 5 L reactor was flushed with N2 and EtOH (1.75 L, 7 vol) was added. The N2 was allowed to flow through the reactor while the following additions were made. Boc- CBA (25Og, 1.08 mol) was added to the EtOH and the temperature was raised to 55 0C. After almost complete dissolution, triethylamine (525 mL, 3.5 eq.) was added, and then a 30% w/w solution OfNH2OMe hydrochloride in water (599 g, 2 eq.) was added drop-wise at a rate of ~20 mL/min. (the NH2OMe salt solution used had a 5% wt. excess of HCl in it so 3 eq. of base was needed to neutralize all the HCl in the reagent). A small exotherm was noted, and during the addition, the solution cleared.alpha-Mercaptoacetic acid (77mL, 1 eq.) was added to produce a slightly opaque mixture of total volume ~3 L. The mantle was heated carefully to 90 0C, and when reflux (internal temp = 78 C) was obtained, the N2 was turned off and the reaction stirred overnight.After 21 hours of stirring at reflux, the reaction was at 96% conversion (HPLC column: Symmetry Shield RP8, 3.5 mum, 50 mm; 230 nm - see Example 3 for more details). The reaction mixture was then cooled to 40 0C and acetone (160 mL, 2 eq.) added over one minute. The mixture was allowed to stand for 1 hour in order to quench any remaining NH2OMe. The mixture was then poured into round-bottomed flasks and the solvent removed by rotary evaporation at 40 0C under vacuum. The remaining residues were dissolved in 3 L of a 2:1 mixture of nBuOAc: H2O and placed in a reactor at 25 0C (total volume = 4.5 L) and stirred for 10 minutes for efficient mixing of the layers.After the phases separated on standing, the aqueous layer (2 L, pH 6) was removed. The organic layer was washed with 1 L of water and the aqueous layer removed (pH=4). EPO <DP n="18"/>This was followed by a wash with a solution OfK2CO3 (297 g, 2 eq.) in 1 L of water (this helps remove the mercaptoacetic acid). The basic water layer was removed and a final wash with 1 L of water was performed. After removal of the aqueous layer, the organic layer was removed from the reactor and stored overnight (total vol -2.3 L). The organic layer was azeotropically dried by removal of approximately half of the nBuOAc (925 mL) on a rotary evaporator. The resulting mixture was placed in a reactor (mantle temp. = 30 C) and 425 mL of nBuOAc was added (total volume of nBuOAc = 2 L - 0.925 + 0.425 = 1.5 L = 6 vol). This was followed by addition of 440 mL (1.75 vol.) of EtOH. The mixture was heated to 30 C to obtain a solution of Boc-Pab(OMe).The above reaction can be repeated using n-butanol as solvent in place of ethanol.The Boc-CBA obtained by the step 1 reaction above can also be used without isolation or purification in the step 2 methoxyamidation reaction.

References: [1]Patent: WO2006/90153,2006,A1 .Location in patent: Page/Page column 15-17.

30
[ 24424-99-5 ]
[ 15996-76-6 ]
[ 66389-80-8 ]

Yield	Reaction Conditions	Operation in experiment
99.5%		Triethylamine (4.932 mL, 35.583 mmol) was added to solution of 4-(aminomethyl)benzonitrile hydrochloride (5.000 g, 29.652 mmol) in dichloromethane (20 mL) at the room temperature, and the mixture was stirred for 10 mm at the same temperature. The reaction mixture was treated at the same temperature with Di-tert-butyl dicarbonate (6.795 g, 31.135 mmol) and stuffed for additional 5 hr. Then, water was added to the reaction mixture, followed by extraction with dichloromethane. The organic layer was washed with aqueous saturated sodium chloride solution, dried with anhydrous Mg504, filtered, and concentrated in vacuo. The title compound was used without further purification (tert-butyl (4-cyanobenzyl)carbamate, 6.850 g, 99.5 %, whtie solid).
95%	With triethylamine; In dichloromethane; at 0 - 20℃; for 16h;	4-(Aminomethyl)benzonitrile hydrochloride 1 (2.82 g, 16.7 mmol) and triethylamine (4.7 mL, 33.7 mmol) were dissolved in anhydrous CH2C12 (50 mL) at 0 C. To this stirred solution was added di-tert-butyl dicarbonate (4.38 g, 20.1 mmol), and the reaction allowed to warm to room temperature and stirred for 16 hours. The reaction mixture was evaporated in vacuo, and the residue was redissolved in diethyl ether (50 mL), which was washed successively with 0.5 M aq. HC1 (2 x 25 mL), saturated NaHCO3 (2 x 25 mL) and brine (25 mL). The organic layer was dried with Mg504, filtered and evaporated in vacuo to give an off-white solid. The residue was purified by flash column chromatography (Hexanes/EtOAc = 10/1) to afford tert-butyl (4- cyanobenzyl) carbamate 2 (3.69 g, yield 95 %) as a colorless solid. It was further characterized according to the literature procedure (4). Figures ]3A-]3B show ?H-NMR and ?3C-NMR spectra, respectively.
94%	With sodium carbonate; In dichloromethane; at 0 - 20℃;	(1) To a solution of 4-aminomethylbenzonitrile hydrochloride (n-1) (5.00 g, 29.7 mmol) in dichloromethane(167 mL), sodium carbonate (7.54 g, 71.2 mmol) was added. The reaction mixture was cooled to 0 C. and di-tert-butyl dicarbonate (7.57 mL, 32.6 mmol) was added; the resulting mixture was brought to room temperature at which it was stirred overnight. To the reaction mixture, water was added and extraction was conducted with ethyl acetate. The organic layer was successively washed with water and saturated brine and dried over anhydrous sodium sulfate. The solvents were distilled off under reduced pressure and the residue was purified by silica gel (NH) column chromatography (n-hexane:ethyl acetate=1:1) to give tert-butyl 4-cyanobenzylcarbamate (n-2) (amount, 6.48 g; yield, 94%).

94%	With sodium carbonate; In dichloromethane; at 0 - 20℃;	To a solution of 4-aminomethylbenzonitrile hydrochloride (n-1) (5.00 g, 29.7 mmol) in dichloromethane(167 mL), sodium carbonate (7.54 g, 71.2 mmol) was added. The reaction mixture was cooled to 0C and di-tert-butyl dicarbonate (7.57 mL, 32.6 mmol) was added; the resulting mixture was brought to room temperature at which it was stirred overnight. To the reaction mixture, water was added and extraction was conducted with ethyl acetate. The organic layer was successively washed with water and saturated brine and dried over anhydrous sodium sulfate. The solvents were distilled off under reduced pressure and the residue was purified by silica gel (NH) column chromatography (n-hexane:ethyl acetate = 1:1) to give tert-butyl 4-cyanobenzylcarbamate (n-2) (amount, 6.48 g; yield, 94%).
80%	With sodium hydroxide; In water; for 16h;	Intermediate 28: tert-butyl {4-[amino(hvdroxyirnino)methyllbenzyl}carbamateStep 1: tert-butyl 4-cyanobenzylcarbamate To a solution of 4-cyanobenzylamine hydrochloride (1.05 g; 6.25 mmol) in water (10 mL) was added sodium hydroxide (0.75 g; 18.75 mmol) and di-tert-butyldicarbonate (1 .49 g; 6.87 <n="114"/>mmol) and the mixture was stirred for 16 hours. The solid was collected by filtration and dried in a vacuum oven at 40C for 48 hours. The title compound was isolated as a white solid (1 .35 g; 80%). 1H NMR: (CDCI3, 400MHz) delta 7.62 (2H, d, J = 8.1 Hz), 7.39 (2H, d, J = 8.0 Hz), 4.97 (1 H, s), 4.37 (2H, d, J = 6.2 Hz), 1.46 (9H, s).
	With sodium hydroxide; In 1,4-dioxane; water; at 0℃; for 4.16667h;	100 g (0.593 mol) of 4-cyanobenzylamine×HCl were dissolved in 1.2 l of dioxane and 600 ml of 2 N NaOH. 142.3 g (0.652 mol) of di(tert-butyl)pyrocarbonates were added in two portions over 10 min at 0 C. The pH was adjusted to 9-10 by adding 2 N NaOH, and the mixture was stirred for a further 4 h. The solvent was removed in vacuo, and the residue was taken up with ethyl acetate, washed 3× each with 5% KHSO4 and NaCl-saturated water and then dried over Na2SO4. The solvent was removed in vacuo (white solid). Yield: 132.6 g (0.57 mol) of white solid, HPLC: 51.6% B
	With triethylamine; In dichloromethane;	Synthesis of tert-butyl(4-cyanobenzyl)carbamate (7) (0149) 4-Cyanobenzylamine HCl (5.00 g, 29.7 mmol, 1.0 eq) was suspended in CH2Cl2 and NEt3 (10.3 mL, 74.1 mmol, 2.5 eq) were added to obtain a clear solution. Boc2O (8.86 mL, 38.6 mmol, 1.3 eq) was added and the solution was stirred overnight. The reaction mixture was diluted to a total volume of 100 mL with CH2Cl2 and washed with 1 M HCl (3×15 mL) and sat. NaHCO3 (3×15 mL). The organic layer was dried over MgSO4 and concentrated under reduced pressure. (0150) 1H NMR (500 MHz, CDCl3) delta 7.58-7.52 (m, 2H), 7.35-7.29 (m, 2H), 4.88 (s, 1H), 4.30 (d, J=6.3 Hz, 2H), 1.39 (s, 9H). (0151) 13C NMR (126 MHz, CDCl3) delta 156.2, 145.0, 132.8, 128.2, 119.1, 111.6, 80.5, 44.6, 28.8. (0152) HRMS (ESI): m/z calc. for C13H16N2NaO2+: 255.1104. found: 255.1110 (Delta=-2.0 ppm).

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[ 66389-80-8 ]

References: [1]Helvetica Chimica Acta,2008,vol. 91,p. 654 - 664.

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References: [1]Chemistry - A European Journal,2010,vol. 16,p. 4557 - 4566.

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[ 1321591-58-5 ]

References: [1]Chemical Communications,2011,vol. 47,p. 8322 - 8324.

34
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[ 1314538-55-0 ]
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References: [1]Organic Letters,2011,vol. 13,p. 3956 - 3959.

35
tert-butyl ((4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)methyl)carbamate [ No CAS ]
[ 66389-80-8 ]

References: [1]Organic Letters,2011,vol. 13,p. 3956 - 3959.

Historical Records

Technical Information

• Acyl Group Substitution • Alkyl Halide Occurrence • Blaise Reaction • Bouveault-Blanc Reduction • Buchwald-Hartwig C-N Bond and C-O Bond Formation Reactions • Catalytic Hydrogenation • Chan-Lam Coupling Reaction • Complex Metal Hydride Reductions • Ester Cleavage • Hydride Reductions • Lawesson's Reagent • Leuckart-Wallach Reaction • Mannich Reaction • Petasis Reaction • Preparation of Aldehydes and Ketones • Preparation of Amines • Reactions of Amines • Reactions of Benzene and Substituted Benzenes • Reactions with Organometallic Reagents • Ritter Reaction • Specialized Acylation Reagents-Carbodiimides and Related Reagents • Specialized Acylation Reagents-Ketenes • Specialized Acylation Reagents-Vilsmeier Reagent • Thorpe-Ziegler Reaction • Ugi Reaction

Related Functional Groups of
[ 66389-80-8 ]

Aryls

A545494 [849237-14-5]

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A101402 [123986-64-1]

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Amides

A545494 [849237-14-5]

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A153751 [174799-52-1]

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A199716 [226070-69-5]

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Amines

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1-(N-Boc-aminomethyl)-4-(aminomethyl)benzene

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A101402 [123986-64-1]

tert-Butyl 4-(hydroxymethyl)benzylcarbamate

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A153751 [174799-52-1]

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A199716 [226070-69-5]

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CAS No.: 66389-80-8

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