* 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.
With sodium hydrogencarbonate In tetrahydrofuran; water at 0 - 20℃;
To a stirred mixture of 5-amino-1 -pentanol (48.5 mmol, 5.0 g) and sodium bicarbonate (145.4 mmol, 12.2 g) in water (26 mL) at 05C, a solution of benzyl chloroformate (63.1 mmol, 9.0 mL) in anh THF (26 mL) was added dropwise. After stirring at room temperature overnight, reaction mixture was diluted with EtOAc and H20. The organic layer was separated, washed with brine (2x30 mL), dried over anh MgS04, filtered and solvent removed under reduced pressure. The crude was dispersed in the minimum amount of cyclohexane and the resulting solid was filtered and dried under vacuum. The title compound was obtained as a white solid (8.2 g, 71 percent). 1 H NMR (400 MHz, CDCI3) δ 7.35 (m, 5H), 5.09 (2H, s), 4.8 (1 H, brs), 3.65 (2H, m), 3.20 (2H, m), 1 .50-1 .58 (6H, m), 1 .39 (2H, m).
70%
With sodium hydroxide In water at 20℃; for 22 h;
To a stirred solution of 5-aminopentanol S1 (6.00 g, 0.058 mol, 1.0 eq.) in 1 M aq. NaOH (65 mL) was added CbzCl (9.1 mL, 0.064 mol, 1.1 eq.) in a dropwise fashion. The reaction mixture was stirred at room temperature for 22 h during which time a white precipitate formed. The reaction mixture was filtered in vacuo and washed with water (20 mL) to afford the crude product which was purified by recrystallisation (EtOAc/c-Hex) affording S2 (9.67 g, 70 percent) as a white solid. Rf = 0.2 (c-Hex/EtOAc; 1:1); IR (NaCl, dep. from CH2Cl2) 3320, 2935, 1692, 1543, 1455, 1375, 1272, 1053, 1028 cm-1; HRMS (ESI): calcd. for [C13H19NO3 +Na]+ 260.1263, found 260.1258; 1H NMR (CDCl3, 400 MHz): d 1.33 – 1.47 (m, 2H), 1.48 – 1.65 (m, 4H), 3.21 (app. q, J = 6.4 Hz, 2H), 3.64 (t, J = 6.4 Hz, 2H), 4.78 (br s, 1H), 5.09 (s, 2H), 7.28 – 7.40 (m, 5H) ppm; 13C NMR (CDCl3, 100 MHz): d 22.9 (CH2), 29.8 (CH2), 32.2 (CH2), 40.9 (CH2), 62.7 (CH2), 66.6 (CH2), 128.1 (CH), 128.1 (CH), 128.5 (CH), 136.6 (C), 156.4 (C) ppm. Data are consistent with those reported in literature.
Reference：
[1] Journal of the American Chemical Society, 2006, vol. 128, # 12, p. 4058 - 4073
[2] Chemical Communications, 2010, vol. 46, # 48, p. 9119 - 9121
[3] Chemistry - A European Journal, 2010, vol. 16, # 6, p. 1754 - 1760
[4] European Journal of Organic Chemistry, 2011, # 12, p. 2346 - 2353
[5] Journal of Medicinal Chemistry, 2002, vol. 45, # 23, p. 5098 - 5111
[6] Chemical Communications, 2006, # 20, p. 2156 - 2158
[7] Patent: WO2013/149996, 2013, A1, . Location in patent: Page/Page column 75
[8] Tetrahedron Letters, 2018, vol. 59, # 17, p. 1627 - 1629
[9] Organometallics, 2014, vol. 33, # 21, p. 5940 - 5943
[10] Journal of Medicinal Chemistry, 1991, vol. 34, # 4, p. 1258 - 1271
[11] Journal of Medicinal Chemistry, 1997, vol. 40, # 18, p. 2883 - 2894
[12] Journal of Organic Chemistry, 2004, vol. 69, # 10, p. 3590 - 3592
[13] Journal of Organic Chemistry, 2001, vol. 66, # 3, p. 809 - 823
[14] Bioorganic and Medicinal Chemistry Letters, 2006, vol. 16, # 19, p. 5194 - 5198
[15] Patent: US2006/84617, 2006, A1, . Location in patent: Page/Page column 17
[16] Synthesis (Germany), 2017, vol. 49, # 12, p. 2761 - 2767
2
[ 1927-62-4 ]
[ 501-53-1 ]
[ 87905-98-4 ]
Reference：
[1] European Journal of Organic Chemistry, 2007, # 28, p. 4646 - 4650
3
[ 1346132-35-1 ]
[ 87905-98-4 ]
Reference：
[1] Advanced Synthesis and Catalysis, 2011, vol. 353, # 14-15, p. 2721 - 2730
4
[ 2508-29-4 ]
[ 137160-76-0 ]
[ 87905-98-4 ]
Reference：
[1] Synthesis, 1991, # 9, p. 713 - 716
5
[ 1443034-29-4 ]
[ 87905-98-4 ]
Reference：
[1] Chemical Communications, 2017, vol. 53, # 65, p. 9085 - 9088
With sodium hydrogencarbonate In tetrahydrofuran; water at 0 - 20℃;
97%
With sodium carbonate In dichloromethane; water at 20℃; for 4h;
97%
With sodium hydrogencarbonate In tetrahydrofuran; water at 0 - 20℃;
95%
With dmap; triethylamine In 1,4-dioxane; water at 20℃;
89%
With potassium carbonate In ethanol; water at 0 - 20℃; for 3.5h; Inert atmosphere;
84%
With sodium hydroxide at 0 - 20℃;
82%
With sodium hydroxide at 20℃; for 16h;
71%
With sodium hydrogencarbonate In tetrahydrofuran; water at 0 - 20℃;
Intermediate compound 69: benzyl (5-hydroxypentyl)carbamate
To a stirred mixture of 5-amino-1 -pentanol (48.5 mmol, 5.0 g) and sodium bicarbonate (145.4 mmol, 12.2 g) in water (26 mL) at 05C, a solution of benzyl chloroformate (63.1 mmol, 9.0 mL) in anh THF (26 mL) was added dropwise. After stirring at room temperature overnight, reaction mixture was diluted with EtOAc and H20. The organic layer was separated, washed with brine (2x30 mL), dried over anh MgS04, filtered and solvent removed under reduced pressure. The crude was dispersed in the minimum amount of cyclohexane and the resulting solid was filtered and dried under vacuum. The title compound was obtained as a white solid (8.2 g, 71 %). 1 H NMR (400 MHz, CDCI3) δ 7.35 (m, 5H), 5.09 (2H, s), 4.8 (1 H, brs), 3.65 (2H, m), 3.20 (2H, m), 1 .50-1 .58 (6H, m), 1 .39 (2H, m).
70%
With sodium hydroxide In water at 20℃; for 22h;
Benzyl (5-hydroxypentyl)carbamate S2
To a stirred solution of 5-aminopentanol S1 (6.00 g, 0.058 mol, 1.0 eq.) in 1 M aq. NaOH (65 mL) was added CbzCl (9.1 mL, 0.064 mol, 1.1 eq.) in a dropwise fashion. The reaction mixture was stirred at room temperature for 22 h during which time a white precipitate formed. The reaction mixture was filtered in vacuo and washed with water (20 mL) to afford the crude product which was purified by recrystallisation (EtOAc/c-Hex) affording S2 (9.67 g, 70 %) as a white solid. Rf = 0.2 (c-Hex/EtOAc; 1:1); IR (NaCl, dep. from CH2Cl2) 3320, 2935, 1692, 1543, 1455, 1375, 1272, 1053, 1028 cm-1; HRMS (ESI): calcd. for [C13H19NO3 + Na]+ 260.1263, found 260.1258; 1H NMR (CDCl3, 400 MHz): d 1.33 - 1.47 (m, 2H), 1.48 - 1.65 (m, 4H), 3.21 (app. q, J = 6.4 Hz, 2H), 3.64 (t, J = 6.4 Hz, 2H), 4.78 (br s, 1H), 5.09 (s, 2H), 7.28 - 7.40 (m, 5H) ppm; 13C NMR (CDCl3, 100 MHz): d 22.9 (CH2), 29.8 (CH2), 32.2 (CH2), 40.9 (CH2), 62.7 (CH2), 66.6 (CH2), 128.1 (CH), 128.1 (CH), 128.5 (CH), 136.6 (C), 156.4 (C) ppm. Data are consistent with those reported in literature.
65%
With triethylamine In dichloromethane at 20℃; for 5h; Cooling with ice;
42%
With triethylamine In dichloromethane at 0℃; for 16h;
With sodium hydroxide In 1,4-dioxane for 48h; Ambient temperature;
With sodium carbonate
With sodium hydrogencarbonate In methanol; water Heating;
With sodium hydrogencarbonate In tetrahydrofuran; water at 20℃; for 12h;
With TEA In methanol
With N-ethyl-N,N-diisopropylamine at 0 - 20℃; for 19.5h;
4
A solution of 5-amino-1-pentanol (20.07 g), and N,N-diisopropylethylamine (75 mL) in 300 mL of tetrahydrofuran was treated with benzyl chloroformate (31 ml) for 1.5 hours at 0° C. and 18 hours at room temperature. The solvent was removed in vacuo and the residue was extracted into chloroform. The chloroform was removed in vacuo for a wax which was crystallized from ethyl acetate and hexanes to give N-CBZ-5-amino-1-pentanol (26.2 g) as a crystalline solid.
With triethylamine In dichloromethane at 0 - 20℃; for 1h; Inert atmosphere;
Procedure A: Cbz protection.
General procedure: To a stirred solution of the starting material in CH2Cl2, triethylamine and benzylchloroformate were added at 0 °C in an N2 atmosphere. The reaction mixture was stirred for 1 h at room temperature, subsequently quenched by adding a saturated NH4Cl solution at 0 °C, and extracted twice with EtOAc. The combined organic layers were washed with brine, dried over MgSO4, filtered and concentrated in vacuo. The residue was purified using flash chromatography on silica gel to yield N-Cbz amino alcohol.
With sodium hydroxide In water; acetone at 20℃; for 4h;
3.3.1 Example 3:N-fluorenylmethoxycarbonyl-N'-benzyloxycarbonyl-homolysine
Step 3.1:Add 6-amino-1-hexanol (10.0 g, 97 mmol) to a 200 mL three-necked flask.Then add acetone (60 mL) and water (60 mL);Cbz-OSu (24.9 g, 0.1 mol) and sodium hydroxide (4.8 g, 0.12 mol) were added.After stirring at room temperature for 4 hours, the solvent was distilled off by a rotary evaporator.Add 200 mL of ethyl acetate and separate the organic phase.Wash with water (100 mL) and saturated brine (100 mL),Dry over anhydrous sodium sulfate. The filtrate was spun dry to give a colorless oil.Compound 9(1-Cbz amino-5-pentanol, 22.3 g, yield 100%),Used directly in the next reaction;
With carbon tetrabromide; triphenylphosphine In dichloromethane at 20℃;
82%
With carbon tetrabromide; triphenylphosphine In dichloromethane at 0 - 20℃;
72%
With N-Bromosuccinimide; triphenylphosphine In dichloromethane at 0 - 20℃; for 3h;
With bromine; N-ethyl-N,N-diisopropylamine; lithium bromide In dichloromethane at 0 - 20℃; for 20h;
5
A solution of triphenylphosphine (11.05 g), lithium bromide (10.98 g) and bromine (2.2 mL) in methylene chloride at 0° C. was treated dropwise with a solution of N-CBZ-5-amino-1-pentanol (10.0 g) and N,N-diisopropylethylamine (17 mL) in methylene chloride. After stirring 20 hours at room temperature, the mixture was washed with water and extracted into methylene chloride. The solvent was removed in vacuo for a wax. The wax was purified on silica gel, eluting with a gradient of ethyl acetate in hexanes. Fractions containing product (TLC Rf 0.94, EtOAc/Hex 1:1) were combined, and the solvent was removed to afford 7.23 g of N-CBZ-5-amino-1-bromopentane as an oil.
Chemistry
Pharmaceutical Intermediates
Inhibitors/Agonists
Material Science
For Research Only
110K+ Compounds
Competitive Price
1-2 Day Shipping
