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USD 41.00
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Structure of 28920-43-6 * Storage: {[proInfo.prStorage]}
Reference：
[1] Journal of Organic Chemistry, 2010, vol. 75, # 5, p. 1386 - 1392
2
[ 449806-69-3 ]
[ 186581-53-3 ]
[ 28920-43-6 ]
[ 103478-62-2 ]
Reference：
[1] Journal of Organic Chemistry, 2007, vol. 72, # 10, p. 3723 - 3728
3
[ 56-86-0 ]
[ 28920-43-6 ]
[ 104091-09-0 ]
Reference：
[1] Journal of the Chinese Chemical Society, 2011, vol. 58, # 4, p. 509 - 515
[2] Soft Matter, 2011, vol. 7, # 19, p. 8913 - 8922
4
[ 28920-43-6 ]
[ 104091-09-0 ]
Reference：
[1] Synlett, 2011, # 14, p. 2013 - 2016
5
[ 28920-43-6 ]
[ 3105-95-1 ]
[ 101555-63-9 ]
Yield
Reaction Conditions
Operation in experiment
1.41 g
With sodium carbonate In 1,4-dioxane; water at 0 - 20℃; for 16 h;
To a stirred mixture of (S)-piperidine-2-carboxylic acid (1.0 g, 7.75 mmol) and Na2C03 (1.65 g, 15.50 mmol) in water (10 mL) was added a solution of FMOC-C1 (3.0 g, 11.63 mmol) in 1,4-dioxane (10 mL) dropwise at 0°C and the reaction mixture was stirred at room temperature for 16 h. The reaction mixture was diluted with water (50 mL) and washed with MTBE (25 mL). The aqueous layer was acidified with 1M aqueous HC1 (10 mL) to pH 2 and extracted with EtOAc (3 x 50 mL). The combined organic extracts were washed with brine solution (50 mL), dried over anhydrous a2S04, filtered and concentrated to afford the title compound (1.41 g) as an off-white solid. The crude product was used in the next step without purification
Reference：
[1] Bioorganic and Medicinal Chemistry Letters, 2014, vol. 24, # 4, p. 1111 - 1115
[2] Journal of the American Chemical Society, 2006, vol. 128, # 11, p. 3838 - 3847
[3] Patent: WO2013/148478, 2013, A1, . Location in patent: Page/Page column 23
6
[ 28920-43-6 ]
[ 15912-30-8 ]
[ 101555-63-9 ]
Reference：
[1] Journal of Organic Chemistry, 1992, vol. 57, # 16, p. 4394 - 4400
7
[ 28920-43-6 ]
[ 25691-37-6 ]
[ 117106-21-5 ]
Reference：
[1] Journal of Organic Chemistry, 1991, vol. 56, # 14, p. 4347 - 4354
8
[ 28920-43-6 ]
[ 109425-55-0 ]
Reference：
[1] Chemical and Pharmaceutical Bulletin, 2001, vol. 49, # 9, p. 1189 - 1191
9
[ 28920-43-6 ]
[ 109425-55-0 ]
Reference：
[1] Protein and Peptide Letters, 2010, vol. 17, # 7, p. 889 - 898
The compound 2 (2g, 7.60mmol) was dissolved in 10percent Na2CO3, and the Fmoc-Cl (2.94g, 11.4mmol) was added slowly, which was mixed with THF (7mL). After stirring overnight, 10percent citric acid was added to adjust PH 4 ~ 5. The THF was removed under reduced pressure and the residual solution was extracted by CH2Cl2. After washing successively with saturated NaCl solution, the organic phase was dried over anhydrous Na2SO4 and concentrated, the residue was purified by silica gel column chromatography (550mg, 15percent). 1H NMR (400 MHz, DMSO-d6 ) δ 7.85 (d, J = 7.5 Hz, 2H), 7.77 ~7.61 (m, 3H), 7.37 (t, J = 7.5 Hz, 2H), 7.28 (t, J =7.4 Hz, 2H), 4.32~4.14 (m, 3H), 4.08 (qd, J = 8.8, 4.6 Hz, 1H), 2.86 (dt, J = 24.4, 10.2 Hz, 1H), 2.70(ddd, J = 15.2, 9.6, 5.6 Hz, 1H), 2.55 ~ 2.41 (m, 2H), 2.23 (t, J = 7.3 Hz, 2H), 1.68 (dd, J = 8.4, 6.1 Hz, 2H), 1.33 (s, 9H). 13C-NMR (100 MHz, DMSO-d6 ): δ172.86, 172.31, 156.54, 144.32, 141.26, 141.24, 128.17, 127.59, 125.84, 125.80, 120.64, 80.13, 66.26, 54.58, 47.14, 34.11, 33.05, 33.04, 31.15, 28.24, 25.03.
10%
With sodium carbonate In tetrahydrofuran at 20℃;
Preparation of Compound 21: Compound 4 (2 g, 7.6 mmol) was dissolved with 10 ml of 10percent Na 2 CO 3 solution, Fmoc-Cl (2.94 g, 11.4 mmol) dissolved in THF was added, reacted overnight at room temperature, and the pH was adjusted with 10percent citric acid. 5, THF was removed under reduced pressure, extracted with CH2Cl2, the organic phase was washed with saturated NaCl solution, and dried under reduced pressure to give a brown yellow oil product 21 (200 mg, yield: 10percent);
Reference：
[1] Bioorganic and Medicinal Chemistry Letters, 2018, vol. 28, # 14, p. 2375 - 2378
[2] Patent: CN107628975, 2018, A, . Location in patent: Paragraph 0142; 0143; 0144; 0145; 0146; 0147
17
[ 28920-43-6 ]
[ 25840-83-9 ]
[ 111061-56-4 ]
Reference：
[1] Liebigs Annalen der Chemie, 1987, p. 1025 - 1030
18
[ 28920-43-6 ]
[ 45125-00-6 ]
[ 104091-08-9 ]
Reference：
[1] Journal of Organic Chemistry, 1986, vol. 51, # 24, p. 4590 - 4594
Reference：
[1] Indian Journal of Chemistry, Section B: Organic Chemistry Including Medicinal Chemistry, 2001, vol. 40, # 1, p. 70 - 74
21
[ 28920-43-6 ]
[ 141-43-5 ]
[ 105496-31-9 ]
Yield
Reaction Conditions
Operation in experiment
87%
at 20℃; for 0.0333333 h; Sonication; Irradiation; Green chemistry
General procedure: Amine (1 mmol) and Fmoc-Cl (1.1 mmol) were placed in a glass tube under neat conditions and were sonicated for a suitable time (as indicated in Tables 1, 2 and 3). All reactions were performed in a water bath at room temperature. After completion of the reaction (as indicated by TLC), 5 cm3 of diethyl ether was added to the mixture. The N-Fmoc derivatives were crystallized and were obtained in good to excellent yields. Purification of the product was accomplished by recrystallization from diethyl ether.
Reference：
[1] Nucleosides and Nucleotides, 1994, vol. 13, # 1-3, p. 255 - 273
[2] Journal of Medicinal Chemistry, 2012, vol. 55, # 2, p. 871 - 882
[3] Journal of Carbohydrate Chemistry, 2012, vol. 31, # 4-6, p. 384 - 419
[4] Russian Journal of Bioorganic Chemistry, 2005, vol. 31, # 4, p. 352 - 356
[5] European Journal of Organic Chemistry, 2008, # 34, p. 5786 - 5797
[6] Green Chemistry, 2011, vol. 13, # 12, p. 3355 - 3359
[7] Journal of the Brazilian Chemical Society, 2016, vol. 27, # 3, p. 546 - 550
[8] Chemical Communications, 2014, vol. 50, # 54, p. 7132 - 7135
[9] Patent: WO2018/149419, 2018, A1, . Location in patent: Paragraph 001283
[10] Tetrahedron Letters, 1993, vol. 34, # 39, p. 6189 - 6192
[11] Tetrahedron Letters, 2002, vol. 43, # 17, p. 3125 - 3128
[12] Patent: US2006/51291, 2006, A1, . Location in patent: Page/Page column 7; 24
[13] Patent: US5599587, 1997, A,
[14] Patent: WO2006/39668, 2006, A2, . Location in patent: Page/Page column 40
[15] Patent: WO2006/105123, 2006, A2, . Location in patent: Page/Page column 50
22
[ 28920-43-6 ]
[ 56-12-2 ]
[ 116821-47-7 ]
Reference：
[1] Chemistry - A European Journal, 1998, vol. 4, # 3, p. 425 - 433
[2] Tetrahedron Letters, 1998, vol. 39, # 28, p. 5117 - 5120
[3] Bioorganic Chemistry, 1996, vol. 24, # 1, p. 50 - 58
[4] Tetrahedron Letters, 2004, vol. 45, # 19, p. 3703 - 3706
[5] Patent: US2003/143591, 2003, A1,
[6] Russian Journal of General Chemistry, 2010, vol. 80, # 12, p. 2572 - 2589
23
[ 28920-43-6 ]
[ 112883-41-7 ]
Reference：
[1] Patent: US5097013, 1992, A,
24
[ 28920-43-6 ]
[ 210345-89-4 ]
[ 1018899-99-4 ]
Reference：
[1] Chemical communications (Cambridge, England), 2001, # 22, p. 2330 - 2331
Reference：
[1] Journal of the American Chemical Society, 2016, vol. 138, # 5, p. 1698 - 1708
[2] Patent: WO2016/138288, 2016, A1, . Location in patent: Page/Page column 124
27
[ 28920-43-6 ]
[ 1172579-62-2 ]
Reference：
[1] Chemistry - A European Journal, 2014, vol. 20, # 21, p. 6526 - 6531
With hydrazine hydrate; In water; acetonitrile; at 0 - 20℃; for 14h;
9-H-Fluoren-9-ylmethyl carbazate (1) (0156) To a well-stirred solution of hydrazine hydrate (19 g, 386 mmol) in 150 mL of CH3CN/H2O (1/1, v/v), a solution of FmocCl (10 g, 38.65 mmol) in 600 mL CH3CN was added dropwise at 0 C. over 2 h. The reaction mixture was then allowed to warm to room temperature and stirred for an additional 12 hours, concentrated in vacuo to 150 mL and filtered to yield the title compound as a white solid, which was washed with water and hexane and dried to a constant weight in vacuo (9.74 g, 99%): mp 172-173 C.; 1H NMR (DMSO) ? 4.08 (brs, 2H), 4.21 (t, J=7.2 Hz, 1H), 4.28 (d, J=7.2 Hz, 2H), 7.32 (t, J=7.4 Hz, 2H), 7.42 (t, J=7.4 Hz, 2H), 7.69 (d, J=7.4 Hz, 2H), 7.89 (d, J=7.4 Hz, 2H), 8.36 (brs, 1H); 13C NMR (DMSO) ?? 47.7, 66.7, 121.1 (2C), 126.3 (2C), 128.1 (2C), 128.7 (2C), 141.7 (2C), 144.9 (2C), 159.2.
99%
With hydrazine; In diethyl ether; at 20℃;Cooling with ice;
Synthesis of compound 7 Synthesis of (9H-fluoren-9-yl)methyl hydrazinecarboxylate (Compound 1): To a round bottom flask containing hydrazine (9.3 g, 0.291 mol) in diethyl ether (anhydrous, 200 mL) at ice bath temperature, was added 9-fluorenylmethyl chloroformate (25 g, 97 mmol) in diethyl ether (anhydrous, 200 mL) dropwise in a two-hour time period. After addition, the reaction was allowed to room temperature and stirred overnight. The reaction was concentrated in vacuo to remove the volatiles. The white solid residue was washed with water (500 mL), filtered and dried to afford compound 1 (24.2 g, 95 mmol, 99 % yield).
98%
With hydrazine hydrate; In diethyl ether; at 0 - 20℃; for 0.5h;
The hydrazine hydrate (48.5 g, 970 mmol) was dissolved in diethyl ether (200 ml).Cooling at 0 C,A cooling solution was obtained, and FMOC-Cl (25 g, 97 mmol) was dissolved in diethyl ether (100 ml).And added dropwise to the cooling solution, stirred for 30 minutes, and then stirred at room temperature overnight.The obtained reaction mixture A was filtered, and the obtained solid was washed with water (3×100ml).The solvent was removed to give A1 (24.1 g, 95 mmol, 98%).
95%
With hydrazine hydrate; In water; acetonitrile; at 0 - 20℃;
At 0 C Fmoc chloride (2 mmol, 517.4 mg) dissolved in acetonitrile (30 mL) is added to hydrazine hydrate (20 mmol, 1 g, 10 equiv) dissolved in 10 mL of a 1/1 mixture water/acetonitrile. The reaction was stirred at 0 C for 2 h (formation of a white precipitate), then allowed to warm up to room temperature and stirred for an additional hour. The mixture was concentrated under vacuo and the precipitate was washed with water, cyclohexane, and then dried under vacuo to afford the pure title compound as a white solid (481 mg, 95%). Mp 174 C (lit. 172-173 C).refPreviewPlaceHolder30Comment1H NMR (DMSO) delta 4.07 (s, 2H), 4.18-4.31 (m, 3H), 7.32 (t, 2H, J=7.4 Hz), 7.41 (t, 2H, J=7.4 Hz), 7.68 (d, 2H, J=7.4 Hz), 7.88 (d, 2H, J=7.4 Hz), 8.34 (s, 1H); 13C NMR (DMSO) delta 46.6, 65.6, 120.1, 125.2, 127.0, 127.6, 140.7, 143.8, 158.2. MS (ESI) m/z: 255.1 [M+H]+.
81%
With hydrazine; In diethyl ether; at 0 - 20℃; for 0.5h;
Fmoc-CI (10 g, 38.7 MMOL) dissolved in diethyl ether (180 mL) was added dropwise to a solution of hydrazine hydrate (3.8 mL, 77 MMOL) in diethyl ether (100 mL) cooled in an ice-bath. White precipitation formed quickly. When all the FMOC-CI was added the resulting white suspension was warmed to rt. and stirred for 30 min. The white solid was isolated by filtration, washed with diethyl ether (x3) and water (x3) and dried in vacuo to give the desired product. Yield : 8 g (81%) ; Rf = 0.2 (PE: EA 1: 1 + a few drops of acetic acid); HPLC: Rt = 4.16 min. (>99%) ; H-NMR (DMSO-D6, 250 MHz) 8 8.34 (br, 1 H), 7.90-7. 88 (d, J = 7.3, 2H), 7.71-7. 68 (d, J = 7.3, 2H), 7.45-7. 29 (m, 4H), 4.30-4. 18 (m, 3H), 4.08 (br, 2H) ; 13C (DMSO-D6, 250 MHz) 8 158.2, 143.8, 140.7, 127.6, 127.0, 125.2, 120.0, 65.6, 46.7 ; ES-MS: mass CALCD for C15H15N202 255.1 (MH+). Found m/z 255.1.
With hydrazine; In diethyl ether; at 0 - 20℃; for 16.5h;
40 Hydrazine (18.0 mL, 213 mmol) was dissolved in 41 diethyl ether (240 mL) at 0 C.A solution of 42 Fmoc chloride (1) (12.0 g, 46.4 mmol) in diethyl ether (240 mL) was added to the hydrazine solution over a 30-minute period. The reaction mixture was stirred at room temperature for 16 h. The solution was evaporated, and 26 water (400 mL) and 15 ethyl acetate (400 mL) were added. The organic phase was washed with water (4×150 mL). The resulting suspension was evaporated. 43 Fmoc-hydrazine (2) was obtained as a white solid (13.92 g, 118%). 1H NMR (300 MHz, CDCl3) delta (ppm) 7.71-7.29 (m, 8H), 6.05 (s, 1H), 4.45 (d, 1H, J=6.8 Hz), 4.23 (t, 1H, J=8.3 Hz), 3.81 (s, 2H). 13C NMR (75.5 MHz, CDCl3) delta (ppm) 143.6, 141.3, 127.8, 127.1, 120.1, 67.3, 47.1 IR (CHCl3) v (cm-1) 1686, 1633, 1506, 1446.
1.92 g
With hydrazine hydrate; In water; acetonitrile; at 20℃; for 12h;
Synthesized according to literature procedures [12,16]. Briefly, a solution of Fmoc-Cl (2.00 g,7.73 mmol) in 120 mL of CH3CN was added dropwise over 2 h at 0 C to a solution of excess hydrazinehydrate (3.8 mL, 78.0 mmol, 10 equiv) in 26 mL of CH3CN/H2O (1:1, v/v). The solution was warmedto room temperature and left stirring for 12 h, prior to being concentrated in vacuo and filtered.The resulting solid was washed with water, followed by hexanes, to give 1.92 g of white solid in 98%yield. The resulting 9H-fluoren-9-ylmethyl hydrazinecarboxylate 3 (1.92 g, 7.55 mmol) was suspendedin acetone (50 mL) and heated at reflux for 2 h. Acetone was evaporated in vacuo and the hydrazoneintermediate was dissolved in THF (50 mL), treated with acetic acid (0.48 mL, 8.39 mmol, 1.1 equiv) andNaBH3CN (521 mg, 8.31 mmol, 1.1 equiv), and stirred for 2 h. The volatiles were removed and the crudewas dissolved in EtOAc (100 mL), washed with 1Maqueous KHSO4 (4 50 mL) and brine (2 50 mL),dried over Na2SO4, and concentrated to give a white solid. The obtained product was dissolved inEtOH and heated for 1 h, followed by evaporation of EtOH to yield N?-isopropyl-fluoren-9-ylmethylcarbazate 4 as a white solid (1.32 g, 59% yield) after column chromatography using a 20-100% gradientof EtOAc in hexanes. NMR (CDCl3) spectra matched literature values [12].
L. Cipolla, M. Rescigno, A. Leone, F. Peri, B. The Ferla, F. Nicotra Bioorg. Med. Chem. 2002, 10, 1639-1646 by protection of commercial O-carboxymethyl-hydroxylamine hemihydrochloride ((H2NOCH2COOH)2. HCl) with 9-fluorenylmethyl chloroformate (Fmoc-Cl) in dioxane in the presence of Na2CO3 (77%) followed by reaction of the acid obtained as an intermediate product (FmocNHOCH2COOH) with N-hydroxysuccinimide in the presence of dicyclohexylcarbodiimide (DCC) in an ethyl acetate/dioxane mixture (yield: 93%). The physical and spectroscopic characteristics of the 2 compounds are described.
With pyridine; In dichloromethane; at 0 - 20℃; for 24h;
Tert-butyl 2-hydroxy-acetate (2.5 g) was dissolved in a mixture of pyridine (15 ml) and dichloromethane (DCM, 30 ml). Then Fmoc-chloride (5 g) in dry DCM (15ml) was added dropwise at 0 C. The reaction mixture was stirred at room temperature for 24 hours. The solvent was removed under vacuum and the residue was redissolved in DCM (40 ml), washed with 1M sodium bicarbonate solution (20 mL) twice, brine solution (20 ml) twice, dried over anhydrous magnesium sulfate and concentrated. The obtained Fmoc-glycolic acid tert-butyl ester (4 g) was dissolved in trifluoroacetic acid (TFA), triisopropylsilane (TIS) and water (95/2.5/2.5, v/v/v, 15 mL) and stirred for 120 min. The solvent was removed under vacuum and the viscous residue was redissolved in 5% sodium bicarbonate solution (150 ml), washed with diethyl ether (75 ml) 3 times. The aqueous solution was then mixed with ethyl acetate (45 mL) and acidified with 40% phosphoric acid to pH = 2 at 0 C. The organic layer was collected and dried with anhydrous magnesium sulfate. The solvent was removed under vacuum to give the final product Fmoc-glycolic acid (Fmoc-GA).
With pyridine; In dichloromethane; at 0 - 20℃; for 24h;
Tert-butyl 2-hydroxy-acetate (2.5 g) was dissolved in a mixture of pyridine (15 ml) and dichloromethane (DCM, 30 ml). Then Fmoc-chloride (5 g) in dry DCM (15ml) was added dropwise at 0 C. The reaction mixture was stirred at room temperature for 24 hours. The solvent was removed under vacuum and the residue was redissolved in DCM (40 ml), washed with 1M sodium bicarbonate solution (20 mL) twice, brine solution (20 ml) twice, dried over anhydrous magnesium sulfate and concentrated. The obtained Fmoc-glycolic acid tert-butyl ester (4 g) was dissolved in trifluoroacetic acid (TFA), triisopropylsilane (TIS) and water (95/2.5/2.5, v/v/v, 15 mL) and stirred for 120 min. The solvent was removed under vacuum and the viscous residue was redissolved in 5% sodium bicarbonate solution (150 ml), washed with diethyl ether (75 ml) 3 times. The aqueous solution was then mixed with ethyl acetate (45 mL) and acidified with 40% phosphoric acid to pH = 2 at 0 C. The organic layer was collected and dried with anhydrous magnesium sulfate. The solvent was removed under vacuum to give the final product Fmoc-glycolic acid (Fmoc-GA).
(a) [(1R)-2-amino-1-methyl-2-oxoethyl]carbamic acid, 9H-fluoren-9-ylmethyl ester A solution of D-Alaninamide hydrochloride (3 g) in 10percent sodium carbonate solution (50 ml) and dioxan (50 ml) was treated with FMOC chloride (6.24 g) in dioxane (40 ml) and allowed to stir overnight. The mixture was diluted with water (500 ml) and the product collected by filtration and dried in vacuo to give 9.0 g of the subtitle compound. MS (ESI) BP 311 (+H)
To a solution of L-serine (methyl ether) hydrochloride (069) (1.0 g, 6.4 mmol) in water/dioxane (1:1, 80 ml) was added sodium hydroxide (768 mg, 19.2 mmol). After the mixture was stirred at room temperature for 30 minutes, it was cooled to 0 ° C., and a solution of 9-fluorenylmethyl chloroformate (1.65 g, 6.4 mmol) in dioxane (16 mL) was added dropwisely. The reaction mixture was allowed to stir at room temperature for another 4 hours. The solvents were then removed, the residue was diluted with water and the pH was adjusted to 1 with 1N HCl, and the aqueous layer was extracted with ethyl acetate (4.x.100 mL). The organic layers were concentrated under reduced pressure and placed under high vacuum to provide (070) (1.8 g) as confirmed by LC/MS (LCRS (MH) m/z: 342.13) which was used without further purification.
A solution of D-Alaninamide hydrochloride (3g) in 10percent sodium carbonate solution (50 ml) and dioxan (50 ml) was treated with FMOC chloride (6.24g) in dioxane (40 ml) and allowed to stir overnight. The mixture was diluted with water (500 ml) and the product collected by filtration and dried in vacuo to give 9.0g of the subtitle compound. MS (ESI) BP 311 (+H)
2-Chloroquinoline-4-carboxylic acid (0.15 g, 0.72 mmol), 4-(aminomethylphenyl)boronic acid (0.16g, 0.87 mmol, 1.2 eq.) and Pd(PPh3)4 (42 mg, 0.036 mmol, 0.05 eq.) were added to a mixture of dioxane (2 mL) and a IM aq. solution OfK2CO3 (2 mL). The reaction mixture was degassed, sealed, and heated in the microwave at 140 0C for 15 min. The reaction mixture was cooled to 0 0C and a solution of (9-fiuorenylmethyl)chloro formate (0.46 g, 1.8 mmol) in dioxane (1 mL) was added dropwise. The reaction mixture was warmed to rt and stirred for 36 h. The reaction mixture was filtered and the solid was washed with DMSO, water and MeOH to give 2-[4-([(9H-fluoren-9-ylmeth- oxy)carbonyl]amino}methyl)phenyl]-quinoline-4-carboxylic acid (0.22 g, 60percent over two steps) as a crude solid, which was used directly in the next step without further purification, m/z 501.3 (M+eta)+.The crude 2-[4-([(9H-fluoren-9-ylmethoxy)carbonyl]-amino}methyl)phenyl]quinoline-4- carboxylic acid was reacted with tert-butyl [?ralpha"5f-4-(aminomethyl)cyclohexyl]methyl}- carbamate using essentially the same procedure as described for Example 1 (Method 1) to give the crude 9H-fluoren-9-ylmethyl [4-(4-[(?ralpha"5f-4-[(?ert-butoxycarbonyl)amino]- methyl} cyclohexyl)methyl]carbamoyl}quinolin-2-yl)benzyl]carbamate, which was used in the next step with no further purification, m/z 725.4 (M+eta)+.The crude 9H-fluoren-9-ylmethyl [4-(4-[(?ralpha"5f-4-[(?ert-butoxycarbonyl)amino]methyl}- cyclohexyl)methyl]carbamoyl}quinolin-2-yl)benzyl]carbamate (0.14 g, 0.19 mmol) was dissolved in DCM (4 mL) and treated with piperidine (1 mL). The reaction mixture was stirred at rt for 5 min. The reaction mixture was concentrated in vacuo to leave a residue. The residue was dissolved in DMSO and purified by etaPLC (Standard method D) to give <n="136"/>the title compound (35 mg, 32percent). 1R NMR (400 MHz, DMSO-J6) delta 8.77 (t, IH), 8.21 (d, 2H), 8.10-8.05 (m, IH), 8.03 (s, IH), 7.77 (t, IH), 7.61-7.46 (m, 4H), 6.74 (t, IH), 3.77 (s, 2H), 3.19 (t, 2H), 2.74 (t, 2H), 1.83 (s, 2H), 1.79 (d, 2H), 1.68 (d, 2H), 1.55-1.45 (m, IH), 1.33 (s, 9H), 1.30-1.23 (m, IH), 1.00-0.76 (m, 4H); m/z 503.4 (M+H)+.
tert-butyl 4-(2-((((9H-fluoren-9-yl)methoxy)carbonyl)(4-bromo-2-chloro-3-methylbenzyl)amino)ethyl)piperazine-1-carboxylate[ No CAS ]
Yield
Reaction Conditions
Operation in experiment
Example 59A tert-butyl 4-(2-((((9H-fluoren-9-yl)methoxy)carbonyl)(4-bromo-2-chloro-3-methylbenzyl)amino)ethyl)piperazine-1-carboxylate To a mixture of Example 10A (3.13 g) in dichloromethane (143 mL) with <strong>[192130-34-0]tert-butyl 4-(2-aminoethyl)piperazine-1-carboxylate</strong> (3.69 g) was added acetic acid (3.84 mL), sodium cyanoborohydride (1.685 g) and methanol (35.7 mL). The mixture was stirred at ambient temperature for 30 minutes. 9-Fluorenylmethyl chloroformate (4.16 g) was added and stirring was continued for another hour. Triethylamine (15 mL) was added, and the material that formed were redissolved with methanol (50 mL). The resulting mixture was concentrated onto silica gel and purification by silica gel chromatography on a CombiFlash® Teledyne Isco system using a Teledyne Isco RediSep® Rf gold 220 g silica gel column (eluting with 0-70percent ethyl acetate/heptane) provided the title compound. LC/MS (APCI) m/z 670.1 (M+H)+.
4-tert-butyl 1-(9H-fluoren-9-ylmethyl) 2-(hydroxymethyl)piperazine-1,4-dicarboxylate[ No CAS ]
Yield
Reaction Conditions
Operation in experiment
79%
With sodium carbonate; In 1,4-dioxane; water; at 0 - 30℃; for 12h;Inert atmosphere;
At 0C , sodium carbonate (0.99g, 9.2mmol) with FMOC chloride (1.5g, 5.6mmol) was added to <strong>[301673-16-5]3-(hydroxymethyl)piperazine-1-carboxylic acid tert-butyl ester</strong> 6a (1.0 g, 4.6mmol) in dioxane (15mL) and water (5mL) was stirred at rt for 12 h.The solvent was removed and concentrated under reduced pressure, the residue was dissolved in ethyl acetate (50 mL), separated, the organic phase was washed with saturated sodium chloride solution (20mL), dried over anhydrous sodium sulfate, filtered and concentrated, the residue was purified by silica gel column chromatography Analysis [petroleum ether / ethyl acetate (v / v) = 3/1] to give the title compound 6b (1.6g, 79% yield) as a colorless oil.
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