| 99% |
With triethylamine; In dichloromethane; at 20℃; for 2h; |
Step 1: Synthesis of tert-butyl N-[(lS)-l-(4-bromophenyl)ethyl]carbamate (O)[0419] To a stirred mixture of (lS)-l-(4-bromophenyl)ethan-l -amine (N, 10.0 g, 49.98 mmol) in dichloromethane (100 mL) was added Et3N (10.0 g, 99.01 mmol) and (Boc)20 (13.0 g, 59.63 mmol). The resulting mixture was stirred at rt for 2 h. The bulk of solvent was then removed under reduced pressure to give a crude residue, which was purified by flash silica gel chromatography (eluent: ethyl acetate/petroleum ether, v: v = 1: 10) to give O (yield: 99%) as a white solid. |
| 99% |
With triethylamine; In dichloromethane; at 20℃; for 2h; |
To a stirred mixture of (1S)-1-(4-bromophenyl)ethan-1-amine (N, 10.0 g, 49.98 mmol) in dichloromethane (100 mL) was added Et3N (10.0 g, 99.01 mmol) and (Boc)2O (13.0 g, 59.63 mmol). The resulting mixture was stirred at rt for 2 h. The bulk of solvent was then removed under reduced pressure to give a crude residue, which was purified by flash silica gel chromatography (eluent: ethyl acetate/petroleum ether, v:v=1:10) to give O (yield: 99%) as a white solid. |
| 98% |
With triethylamine; In dichloromethane; at 18 - 25℃; for 1h; |
A mixture of [(1S)-1-(4-bromophenyl)ethyl]amine (10.00 g, 50.0 mmol) and di-tert-butyl dicarbonate (11.45 g, 52.5 mmol), triethylamine (7.66 mL, 55.0 mmol) in dichloromethane (200 mL) was stirred at room temperature for 1 hour. The mixture was diluted with dichloromethane (500 mL) and washed with 1 M hydrochloric acid (300 mL), saturated sodium hydrogen carbonate aqueous (300 mL), and brine (300 mL). The organic layer was dried over magnesium sulfate, and concentrated under reduced pressure. The residue was washed with cold hexane to afford 14.73 g (98%) of the title compounds as white solids: 1H-NMR (CDCl3) 7.47-7.42 (2H, m), 7.18 (2H, d, J=8.4 Hz), 5.30 (2H, br.s), 1.41 (12H, br.s) |
| 98% |
With triethylamine; In dichloromethane; at 20℃; for 1h; |
STEP 3. tert-Butyl rl1 S)-1-(4-bromophenyl)ethvllcarbamate; A mixture of [(1 S)-l-(4-bromophenyl)ethyljamine (10.00 g, 50.0 mmol) and di-tert-butyl dicarbonate (11.45 g, 52.5 mmol), triethylamine (7.66 mL, 55.0 mmol) in dichloromethane (200 mL) was stirred at room temperature for 1 hour. The mixture was diluted with dichloromethane (500 mL) and washed with 1 M hydrochloric acid (300 mL), saturated sodium hydrogen carbonate aqueous (300 mL), and brine (300 mL). The organic layer was dried over magnesium sulfate, and concentrated under reduced pressure. The residue was washed with cold hexane to afford 14.73 g (98%) of the title compound as white solids: ¹H-NMR (COCl3) No. 7.47-7.42 (2H, m), 7.18 (2H, d, J = 8.4 Hz), 5.30 (2H, br. s), 1.41 (12H, br.s) |
| 98% |
With triethylamine; In dichloromethane; at 20℃; for 1h; |
EXAMPLE 5 4-[(1S)-1-([5-FLUORO-2-(4-FLUOROPHENOXY)PYRIDIN-3- YLLCARBONYL} AMINO) ETHYLLBENZOIC ACID STEP 1. TERT-BUTYL R (LS)-L- (4-BROMOPHENYL) ETHYLLCARBAMATE; A mixture of [ (IS)-I- (4-BROMOPHENYL) ethyl] amine (10.00 g, 50.0 mmol) and di-tert- butyl dicarbonate (11.45 g, 52.5 mmol), triethylamine (7.66 mL, 55.0 mmol) in dichloromethane (200 mL) was stirred at room temperature for 1 h. The mixture was diluted with dichloromethane (500 mL) and washed with 1 N hydrochloric acid (300 ML), saturated sodium hydrogen carbonate aqueous (300 mL), and brine (300 ML). The organic layer was dried over magnesium sulfate, and concentrated under reduced pressure. The residue was washed with cold hexane to afford 14.73 g (98%) of the title compounds as white solids : H-NMR (CDCL3) o 7.47-7. 42 (2H, m), 7.18 (2H, d, J = 8.4 Hz), 5.30 (2H, br. s), 1.41 (12H, br. s). |
| 98.7% |
With sodium hydrogencarbonate; In water; ethyl acetate; at 5℃; for 2h; |
To a mixture of (5)-l-(4-bromophenyl)ethanamine (3.98 g, 19.9 mmol) and NaHC( (1.24 g, 14.8 mmol) in H20 (10 mL) and ethyl acetate (10 mL) was added (Boc)20 (5.20 g, 23.8 mmol) at 5C. The reaction was continued to react for 2 h. TLC showed reaction was complete. The reaction mixture was filtered. The solid was collected and suspended in a mixture of hexane (10 mL) and H20 (10 mL) for 0.5 h. The mixture was filtered and the solid was collected and dried in oven at 50C to afford the title compound as white solid (5.9 g, 98.7%). ^ MR (400 MHz, DMSO-d6): delta 1.28 (d, J = 7.2 Hz, 3H), 1.36 (s, 9H), 4.55-4.60 (m, 1H), 7.25 (d, J = 8.4 Hz, 2H), 7.39 (br, 1H), 7.49 (d, J = 8.4 Hz, 2H). |
| 98.7% |
With sodium hydrogencarbonate; In water; ethyl acetate; at 5℃; for 2h; |
To a mixture of (S)-1-(4-bromophenyl)ethanamine (3.98 g, 19.9 mmol) and NaHCO3 (1.24 g, 14.8 mmol) in H2O (10 mL) and ethyl acetate (10 mL) was added (Boc)2O (5.20 g, 23.8 mmol) at 5 C. The reaction was continued to react for 2 h. TLC showed reaction was complete. The reaction mixture was filtered. The solid was collected and suspended in a mixture of hexane (10 mL) and H2O (10 mL) for 0.5 h. The mixture was filtered and the solid was collected and dried in oven at 50 C. to afford the title compound as white solid (5.9 g, 98.7%). 1HNMR (400 MHz, DMSO-d6): delta 1.28 (d, J=7.2 Hz, 3H), 1.36 (s, 9H), 4.55-4.60 (m, 1H), 7.25 (d, J=8.4 Hz, 2H), 7.39 (br, 1H), 7.49 (d, J=8.4 Hz, 2H). |
| 98.7% |
With sodium hydrogencarbonate; In water; ethyl acetate; at 5℃; for 2h; |
To a mixture of (S)-l-(4-bromophenyl)ethanamine (3.98 g, 19.9 mmol) and NaHC03 (1.24 g, 14.8 mmol) in H20 (10 mL) and ethyl acetate (10 mL) was added (Boc)20 (5.20 g, 23.8 mmol) at 5C. The reaction was continued to react for 2 hours. TLC showed the reaction was complete. The reaction mixture was filtered. The solid was collected and suspended in a mixture of hexane (10 mL) and H20 (10 mL) for 0.5 h. The mixture was filtered and the solid was collected and dried in oven at 50C to afford the title compound as white solid (5.9 g, 98.7%). 1HNMR (400 MHz, DMSO-d6): delta 1.28 (d, J = 7.2 Hz, 3H), 1.36 (s, 9H), 4.55-4.60 (m, 1H), 7.25 (d, J = 8.4 Hz, 2H), 7.39 (br, 1H), 7.49 (d, J = 8.4 Hz, 2H). |
| 98% |
With triethylamine; In dichloromethane; at 20℃; for 1h;Product distribution / selectivity; |
A mixture of [(1S)-1-(4-bromophenyl)ethyl]amine (10.00 g, 50.0 mmol) and di-tert- butyl dicarbonate (11.45 g, 52.5 mmol), triethylamine (7.66 mL, 55.0 mmol) in dichloromethane (200 mL) was stirred at room temperature for 1 h. The mixture was diluted with dichloromethane (500 mL) and washed with 1 M hydrochloric acid (300 mL), saturated sodium hydrogen carbonate aqueous (300 mL), and brine (300 mL). The organic layer was dried over magnesium sulfate, and concentrated under reduced pressure. The residue was washed with cold hexane to afford 14.73 g (98%) of the title compounds as white solids: H-NMR (CDCl3) No. 7-.47-7.42 (2H, m), 7.18 (2H, d, J=8.4 Hz), 5.30 (2H, br. s), 1.41 (12H, br.s).; A 7'1.}{(at):"::'"s of (at);(at) (at)(at).(at)1-((at).(at)br(at)(at)a(at)(at)(at)r(at)y(at)))(at)(at)hyl](at)am:(at):e (10.00 g, 50.0 mmc.) and ...H..t'(at)0(at),.ui""..:'-,i,I' (at):(at)"""'(at),'"1':(at),(at)..,.,.,.)"{.'O. ,< l .4.5 g, 1i2(at)E -mn-T.(at) No.: .S(at)'.(at).grrs,c 'o..ynr:.7(at),.,(at) I'((at) .a(at) .nn.. 55 (at) -f;,o,"(at)'n' 'i.1..3"J'."(at).".'£-Xll 'I'££ .'m..,? "fizz c'il?iri "£1"" "l5rIil"£'1.-"I '..J. ' ..la,>.'", ' (at)- '=(at)(at)(at)>r4J:"(at)(at)?<:(at)"::.(at)(at):: ':':_(at)(at), n(at).c2. (at)'.: .-:-:(at)(at)(at) ;.:(at).(at)(at):)(at)(at)(at).:::(at)?":: ...(at)::? .:(at)(at)(at):(at)(at)(at) . mixture was diluted with dichloromethane (500 mL) and washed with 1 M hydrochloric acid (300 mL), saturated sodium hydrogen carbonate aqueous (300 mL), and brine (300 mL). The organic layer was dried over magnesium sulfate, and concentrated under reduced pressure. The residue was washed with cold hexane to afford 14.73 g (98%) of the title compound as white solids: ¹H-NMR (CDCl3) No. 7.47-7.42 (2H, m), 7.18 (2H, d, J 8.4 Hz), 5.30 (2H, br.s), 1.41 (12H, br.s; A mixture of [(1S)-1-(4-bromophenyl)ethyl]amine (10.00 g, 50.0 mmol) and di-tert-butyl dicarbonate (11.45 g, 52.5-mmol), triethylamine (7.66 mL, 55.0 mmol) in dichloromethane (200 mL) was stirred at room temperature for 1 hour. The mixture was diluted with dichloromethane (500 mL) and washed with 1 M hydrochloric acid (300 mL), saturated sodium hydrogen carbonate aqueous (300 mL), and brine (300 mL). The organic layer was dried over magnesium sulfate, and concentrated under reduced pressure. The residue was washed with cold hexane to afford 14.73 g (98%) of the title compounds as white solids: (at)H-NMR (CDC13) 87.47-7.42 (2H, m), 7.18 (2H, d, J = 8.4 Hz), 5.30 (2H, br.s), 1.41 (12H, br.s). |
| 96% |
In dichloromethane; at 20℃; for 0.25h; |
STEP 1 : A solution of (1 S)-l-(4-bromophenyl)ethylamine (1Og, 50 mmol) and di-tert-butyl dicarbonate (13 g, 60 mmol) in dichloromethane (80 mL) was stirred at room temperature for 15 hours. Concentration of the reaction mixture afforded a solid residue that was then suspended in diethyl ether (100 mL). The mixture was diluted with hexane (100 mL) and the solid was isolated by filtration, then washed with hexane and dried to afford 14.4 g, 48 mmol (96%) of 1 ,1 - dimethylethyl [(l S)-l-(4-bromophenyl)ethyl]carbamate. 1H NMR (400 MHz, CDCl3): 7.46-7.42 (m, 2H), 7.19-1.76 (m, 2H), 5.29 (s, IH), 4.71 (br s, I H), 1.43- 1.39 (m, 12H). MS (EI) for C13H18BrNO2: 301 (MH+). |
| 96.7% |
With triethylamine; In dichloromethane; at 20℃; for 3h; |
To a solution of (S)-1-(4-bromophenyl)ethan-l -amine (1) (2 g, 10 mmol) in DCM (20 mL) was added di-tert-butyl dicarbonate (2.4 g, 11 mmol) and TEA (1.27 g, 12.4 mmol). The solution was stirred for 3 h at room temperature then washed with water and brine. The organic layer was dried over Na2SO4, filtered and concentrated. Silica gel column chromatography provided (S)-2-(4-bromophenyl)-2-((tert-butoxycarbonyl)amino)ethan-1-ylium (2) as a white solid (2.9 g, 96.7 %). |
| 92% |
With triethylamine; In tetrahydrofuran; dichloromethane; at 0 - 20℃; for 3h; |
Preparative Example 6; Step A; Commercially obtained (S)-(-)-1-(4-bromophenyl)ethylamine (2.0 g, 10.1 mmol) was dissolved in 50 mL dry tetrahydrofuran (THF) and cooled to 0 C. and to this cooled solution was added di-t-butyl dicarbonate (2.0 g, 9.1 mmol) dissolved in 3.0 mL of metheylene chloride (CH2Cl2) followed by Et3N (2.8 mL, 20.1 mmol). The solution was allowed to warm to room temperature. After stirring for 3 hours, the mixture was concentrated and re-dissolved in 100 mL methylene chloride (CH2Cl2). This solution was washed with 1N HCl (2×50 mL) and saturated NaHCO3 (1×50 mL). The CH2Cl2 layer was dried over anhydrous MgSO4, filtered, and concentrated to afford 2.5 g of the desired boc product in 92% yield as a white solid. 1H-NMR delta (CDCl3) 1.35 (br. s, 12H), 4.72 (br. s, 2H), 7.17 (d, 2H), 7.43 (d, 2H). |
| 92% |
With triethylamine; In tetrahydrofuran; dichloromethane; at 0 - 20℃; for 3h; |
Step A. Commercially obtained (S)-(-)-l-(4-bromophenyl)ethylamine (2.0 g, 10.1 mmol) was dissolved in 50 mL dry tetrahydrofuran (THF) and cooled to 0 C and to this cooled solution was added di-t-butyl dicarbonate (2.0 g, 9..1 mmol) dissolved in 3.0 mL of methylene chloride (CH2Cl2) followed by Et3N (2.8 mL, 20.1 mmol). The solution was allowed to warm to room temperature. After stirring for 3 hours, the mixture was concentrated and re-dissolved in 100 mL methylene chloride (CH2Cl2). This solution was washed with IN HCl (2 x 50 mL) and saturated NaHCO3 (1 x 50 mL). The CH2Cl2 layer was dried over anhydrous MgSO4, filtered, and concentrated to afford 2.5 g of the Boc protected product in 92% yield as a white solid. 1H-NMR delta (CDCl3) 1.35 (br. s, 12 H), 4.72 (br. s, 2H), 7.17 (d, 2H), 7.43 (d, 2H). |
| 92% |
With triethylamine; In tetrahydrofuran; dichloromethane; at 0 - 20℃; for 3h; |
Preparative Example 100; Step A; Commercially available (S)-(-)-1-(4-Bromophenyl)ethylamine (2.0 g) was dissolved in dry tetrahydrofuran (50 mL) and cooled to 0 C. and to this cooled solution was added di-t-butyl dicarbonate (2.0 g) dissolved in dichloromethane (3 mul) followed by Et3N (2.8 mL). The solution was allowed to warm to room temperature. After stirring for 3 h, the mixture was concentrated and re-dissolved in dichloromethane (100 mL) This solution was washed with 1N HCl (2×50 mL) and saturated NaHCO3 (50 mL). The organic layer was dried over anhydrous MgSO4, filtered and concentrated to afford the intermediate (2.5 g; 92%) as a colourless solid. 1H-NMR delta (CDCl3) 1.35 (br s, 12H), 4.72 (br s, 2H), 7.17 (d, 2H), 7.43 (d, 2H). |
| 92% |
With triethylamine; In dichloromethane; at 0 - 20℃; for 18.25h; |
To a solution of (lS)-l-(4-bromophenyl)ethanamine (25.0 g, 125 mmol) and BOC anhydride (32.7 g, 150 mmol) in DCM (250 mL) at 0 C, TEA (34.8 mL, 250 mmol) was added. The reaction mixture was stirred at 0 C for 15 min and then 18 h at rt. The mixture was diluted with water (250 mL) and the layers were separated. The aqueous layer was extracted with EtOAc (2 x 100 mL). The combined organic layers were washed with brine (100 mL) then dried (Na2S04), filtered, and concentrated under reduced pressure. The resulting solid was triturated with hexanes (400 mL), filtered and washed with hexanes (500 mL) to afford the title compound as a solid (34.5 g, 92%). MS (ESI) [M-tBu]+ 244.0, 246.0. |
| 85% |
for 0.416667h; |
To a stirring solution of compound (1S)-1-(4-bromophenyl)ethanamine (50 mmol) in 50ml RB and tert-butoxycarbonyl tert-butyl carbonate (50 mmol) was added over period of 20 min and stirring was continued vigorously, After 5 min solid was precipitated out from reaction mass and thus obtained solid25 was filtered and washed with hexane and dried under vacuum. Weight-13 g (85%)1H-NMR (400 MHz, CDCb): 7.45(28, d), 7.18(2H, d), 4.74(1 H, m), 1.40-1.48 (12H, m). |
| 82% |
|
To a solution of (1S)-1-(4-bromophenyl)ethanamine (5 g, 24.99 mmol, 1.0 eq) in dichloromethane (100 mL) was added triethylamine (2.53 g, 24.99 mmol, 1.0 eq) at 0 C. Then the mixture was stirred at 0 C. for 30 minutes. Then di-tert-butyl dicarbonate ester (5.45 g, 24.99 mmol, 1.0 eq) was added, and the mixture and stirred at 0 C. for 30 minutes followed by 20 C. for 2 hours. The mixture was quenched with saturated aqueous sodium bicarbonate (20 mL), diluted with water (50 mL), extracted with dichloromethane (100 mL*2), washed with brine (100 mL), dried over anhydrous sodium sulfate, filtered and concentrated. The residue was stirred with petroleum ether:ethyl acetate (50 mL, v/v=5/1), and then filtered. Tert-butyl N-[(1S)-1-(4-bromophenyl)ethyl]carbamate (6.4 g, 20.68 mmol, 82% yield) was obtained as a white solid. |
| 66% |
With triethylamine; In dichloromethane; at 20℃; for 6h; |
To a solution of (S)-1-(4-bromophenyl)ethan-1-amine (20.0 g, 100.0 mmol) in DCM (200 mL) at 0 C was added triethyl amine (21.6 mL, 120 mmol) followed by the addition of Boc-anhydride (27.5 mL, 150.0 mmol) and the reaction mixture was stirred for 6 h at RT. Then it was quenched with water (200 mL) and extracted with DCM (2 x 500 mL). The combined organic layer was washed with water (200 mL), brine (200 mL), dried over anhydrous sodium sulphate and concentrated under reduced pressure to afford the title compound (23.0 g, 66 %). 1H NMR (400 MHz, DMSO-d6): d 7.51 (d, / = 8.8 Hz, 2H), 7.40 (d, / = 7.4 Hz, 1H), 7.41 (d, / = 7.2 Hz, 2H), 4.60-4.55 (m, 1H), 1.35 (s, 8H), 1.28 (d, / = 6.8 Hz, 4H). |
|
With triethylamine; In tetrahydrofuran; at 0℃; for 2h; |
Step 7: tert-butyl [(lS)-l-(4-bromophenyl)ethyl]carbamate; <n="38"/>To a solution of (5)-(-)- 1 -(4-bromophenyl)ethylamine (Alfa Aesar, 62.9 g, 314 mmol, 98%ee) in THF (500 ml) at O0C was added solid di-ter/-butyl dicarbonate (75.3 g, 345 mmol) followed by triethylamine (88.3 mL, 628 mmol) and the mixture was stirred at O0C for 2h and concentrated in vacuo. The off-white solid thus obtained was washed with ether/hexane and the solid was dried under high vacuum to give the desired product. |
|
With triethylamine; In chloroform; at 0 - 20℃; for 0.5h; |
(1) 2 g of S-(-)-l-(4-bromophenyl)ethylamine was dissolved in 20 mL of chloroform, and 4.18 mL of triethylamine was added. Thereto, 2.62 g of di-tert-butyl dicarbonate was added under an ice- cold condition, and the mixture was stirred for 30 minutes at room temperature. The reaction solution was diluted in 300 mL of ethyl acetate and washed with water and saturated brine in that order, and the resulting organic layer was dried over anhydrous magnesium sulfate. The insolubles were filtered, the filtrate was concentrated under reduced pressure, and the resulting residue was dissolved in a small amount of chloroform and solidified with hexane, to obtain 2.6 g of tert-butyl[(lS)-l-(4- bromophenyl)ethyl]carbamate [1-1] (hereinafter, referred to as the compound [1-1]) as a white solid. |
|
With triethylamine; In chloroform; at 0 - 20℃; for 0.5h; |
2 g of S-(-)-1-(4-bromophenyl)ethylamine was dissolved in 20 mL of chloroform, and 4.18 mL of triethylamine was added thereto. Under an ice-cold condition, 2.62 g of dicarbonic acid di-t-butyl was added, and stirred at room temperature for 30 minutes. The reaction solution was diluted in 300 mL of ethyl acetate, washed with water and saturated brined in the subsequent order, and the obtained organic layer was dried over anhydrous magnesium sulfate. The insolubles were filtered and the filtrate was concentrated under reduced pressure to obtain a residue. The residue was dissolved in a small amount of chloroform and solidified by hexane, to obtain 2.6 g of t-butyl[(1S)-1-(4-bromophenyl)ethyl]carbamate [106-1] as a white solid. |
| 13 g |
for 0.416667h; |
To a stirring solution of compound (1S)-1-(4-bromophenyl)ethanamine (50 mmol) in a 50 mL roundbottom flask and tert-butoxycarbonyl tert-butyl carbonate (50 mmol) was added over period of 20 min and stirring was continued vigorously, After 5 min solid was precipitated out from reaction mass and thus obtained solid was filtered and washed with hexane and dried under vacuum. Weight: 13 g. 1H-NMR (400 MHz, CDCl3): 7.45(2H, d), 7.18(2H, d), 4.74(1H, m), 1.40-1.48 (12H, m). |
| 13 g |
for 0.416667h; |
To a stirring solution of compound (1S)-1-(4-bromophenyl)ethanamine (50 mmol) in a 50 mL roundbottom flask and tert-butoxycarbonyl tert-butyl carbonate (50 mmol) was added over period of 20 min and stirring was continued vigorously, After 5 min solid was precipitated out from reaction mass and thus obtained solid was filtered and washed with hexane and dried under vacuum. Weight: 13 g. 1H-NMR (400 MHz, CDCl3): 7.45(2H, d), 7.18(2H, d), 4.74(1H, m), 1.40-1.48 (12H, m). |
| 13 g |
for 0.416667h; |
Step 1: Preparation of tert-butyl N- 1(1 5?)- 1 -(4-bromophenyl)ethyllcarbamate: To a stirring solution of compound (1S)-1-(4-bromophenyl)ethanamine (50 mmol) in a 50 mL roundbottom flask and tert-butoxycarbonyl tert-butyl carbonate (50 mmol) was added over period of 20mm and stirring was continued vigorously, After 5 mm solid was precipitated out from reaction mass and thus obtained solid was filtered and washed with hexane and dried under vacuum. Weight: 13 g?H-NMR (400 MHz, CDC13): 7.45(2H, d), 7.18(2H, d), 4.74(1H, m), 1.40-1.48 (12H, m) |
| 13 g |
for 0.416667h; |
Ste 1 : Preparation of tert-butyl N-[(lS)-l-(4-bromophenyl)ethyl"|carbamate To a stirring solution of compound (l S)-l-(4-bromophenyl)ethanamine (50 mmol) in a 50 mL roundbottom flask and tert-butoxycarbonyl tert-butyl carbonate (50 mmol) was added over period of 20 min and stirring was continued vigorously, After 5 min solid was precipitated out from reaction mass and thus obtained solid was filtered and washed with hexane and dried under vacuum. Weight: 13 g 'H-NMR (400 MHz, CDC13): 7.45(2H, d), 7.18(2H, d), 4.74(1H, m), 1.40-1.48 (12H, m). |
|
With sodium carbonate; In dichloromethane; water; at 20℃; for 1h; |
To 150 g (735 mmol) (S)-1-(4-bromophenyl)ethylamine in 2 L DCM are added 459 mL (918 mmol) of an aq. Na2CO3 solution (c=2 moVL). To this mixture a solution of 164 g (749 mmol) BOC2O in 350 mL THF is added dropwise at r.t. and stirring is continued for 1 h. After that the mixture is poured onto water and stirred for additional 20 min. The layers are separated, the org. layer is washed with water (2×), dried over Na2SO4 and the solvent is removed in vacuo. [0316] C13H1BrNO2 (M=300.2 g/mol) [0317] ESI-MS: 300/302 [M+H]+ Rf (TLC): 0.90 (silica gel, DCM/MeOH 9/1) |
|
With sodium carbonate; In tetrahydrofuran; dichloromethane; water; at 20℃; |
Example II (SHe/f-Butyl 1 -(4-bromophenyl)ethylcarbamate To 150 g (735 mmol) (S)-1 -(4-bromophenyl)ethylamine in 2 L DCM are added 459 ml_ (918 mmol) of an aq. Na2CO3 solution (c = 2 mol/L). To this mixture a solution of 164 g (749 mmol) BOC2O in 350 ml_ THF is added dropwise at r.t. and stirring is continued for 1 h. After that the mixture is poured onto water and stirred for additional 20 min. The layers are separated, the org. layer is washed with water (2x), dried over Na2SO4 and the solvent is removed in vacuo. Ci3Hi8BrNO2 (M= 300.2 g/mol) ESI-MS: 300/302 [M+H]+ Rf (TLC): 0.90 (silica gel, DCM/MeOH 9/1 ) |
|
With sodium carbonate; In tetrahydrofuran; dichloromethane; water; at 20℃; for 1h; |
Example II (S)-tert-Butyl 1-(4-bromophenyl)ethylcarbamate To 150 g (735 mmol) (S)-1-(4-bromophenyl)ethylamine in 2 L DCM are added 459 mL (918 mmol) of an aq. Na2CO3 solution (c=2 mol/L). To this mixture a solution of 164 g (749 mmol) BOC2O in 350 mL THF is added dropwise at r.t. and stirring is continued for 1 h. Then the mixture is poured onto water and stirred for additional 20 min. The layers are separated, the org. layer is washed with water (2*), dried over Na2SO4, filtered and the solvent is removed in vacuo. C13H18BrNO2 (M=300.2 g/mol) ESI-MS: 300/302 [M+H]+Rf(TLC):0.90 (silica gel, DCM/MeOH 9/1)Rf(TLC):0.90 (silica gel, DCM/MeOH 9/1) |
|
With sodium carbonate; In tetrahydrofuran; at 20℃; for 1h; |
To 1 50 g (735 mmol) (S)-1 -(4-bromophenyl)ethylamine in 2 L DCM are added 459 mL (918 mmol) of an aq. Na2C03 solution (c = 2 mol/L). To this mixture a solution of 164 g (749 mmol) BOC2O in 350 mL THF is added dropwise at r.t. and stirring is continued for 1 h. Then the mixture is poured onto water and stirred for additional 20 min. The layers are separated, the org. layer is washed with water (2x), dried over Na2S04, filtered and the solvent is removed in vacuo. Ci3H18BrN02 (M= 300.2 g/mol) ESI-MS: 300/302 [M+H]+ Rf (TLC):0.90 (silica gel, DCM/MeOH 9/1 ) |
|
With sodium carbonate; In tetrahydrofuran; dichloromethane; water; at 20℃; for 1h; |
To 150 g (735 mmol) (S)-1-(4-bromophenyl)ethylamine in 2 L DCM are added 459 mL (918 mmol) of an aq. Na2CO3 solution (c=2 mol/L). To this mixture a solution of 164 g (749 mmol) BOC2O in 350 mL THF is added dropwise at r.t. and stirring is continued for 1 h. Then the mixture is poured onto water and stirred for additional 20 min. The layers are separated, the org. layer is washed with water (2×), dried over Na2SO4, filtered and the solvent is removed in vacuo.C13H18BrNO2 (M=300.2 g/mol) ESI-MS: 300/302 [M+H]+ Rt (TLC): 0.90 (silica gel, DCM/MeOH 9/1) |
|
With sodium carbonate; In tetrahydrofuran; dichloromethane; water; at 20℃; for 1h; |
Example II (S)-tert-Butyl 1 -(4-bromophenyl)ethylcarbamate To 150 g (735 mmol) (S)-1-(4-bromophenyl)ethylamine in 2 L DCM are added 459 mL (918 mmol) of an aq. Na2C03 solution (c = 2 mol/L). To this mixture a solution of 164 g (749 mmol) BOC20 in 350 mL THF is added dropwise at r.t. and stirring is continued for 1 h. Then the mixture is poured onto water and stirred for additional 20 min. The layers are separated, the org. layer is washed with water (2x), dried over Na2S04, filtered and the solvent is removed in vacuo. C13H 8BrN02(M= 300.2 g/mol) ESI-MS: 300/302 [M+H]+ Rf (TLC):0.90 (silica gel, DCM/MeOH 9/1 ) |
| 15.0 g |
With triethylamine; In dichloromethane; at 20℃; for 2h; |
Into a 250-mL round-bottom flask, was placed (lS)-l-(4-bromophenyl)ethan-l -amine (10.0 g, 49.98 mmol, 1.00 equiv) in dichloromethane (100 mL), triethylamine (10.0 g, 99.01 mmol, 2.00 equiv), di-tert-butyl dicarbonate (13.0 g, 59.63 mmol, 1.20 equiv). The resulting solution was stirred for 2 hours at room temperature. The resulting mixture was concentrated under vacuum. The residue was applied onto a silica gel column with ethyl acetate/petroleum ether (1:10). This resulted in 15.0 g of tert-butyl N-[(lS)-l-(4-bromophenyl)ethyl]carbamate as a white solid. |
| 15.0 g |
With triethylamine; In dichloromethane; at 20℃; for 2h; |
Into a 250-mL round-bottom flask, was placed (1S)-1-(4-bromophenyl)ethan-1-amine (10.0 g, 49.98 mmol, 1.00 equiv) in dichloromethane (100 mL), triethylamine (10.0 g, 99.01 mmol, 2.00 equiv), di-tert-butyl dicarbonate (13.0 g, 59.63 mmol, 1.20 equiv). The resulting solution was stirred for 2 h at room temperature. The resulting mixture was concentrated under vacuum. The residue was applied onto a silica gel column with ethyl acetate/petroleum ether (1:10). This resulted in 15.0 g of tert-butyl N-[(1S)-1-(4-bromophenyl)ethyl]carbamate as a white solid |
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