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[ CAS No. 18938-60-8 ]

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2D
Chemical Structure| 18938-60-8
Chemical Structure| 18938-60-8
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Product Details of [ 18938-60-8 ]

CAS No. :18938-60-8MDL No. :MFCD20264826
Formula :C18H27NO5Boiling Point :476.0±40.0°C at 760 mmHg
Linear Structure Formula :-InChI Key :N/A
M.W :337.41Pubchem ID :15512828
Synonyms :

Computed Properties of [ 18938-60-8 ]

TPSA : 84.9 H-Bond Acceptor Count : 5
XLogP3 : - H-Bond Donor Count : 2
SP3 : 0.56 Rotatable Bond Count : 8

Safety of [ 18938-60-8 ]

Signal Word:WarningClassN/A
Precautionary Statements:P261-P305+P351+P338UN#:N/A
Hazard Statements:H315-H319-H335Packing Group:N/A
GHS Pictogram:

Application In Synthesis of [ 18938-60-8 ]

  • Upstream synthesis route of [ 18938-60-8 ]
  • Downstream synthetic route of [ 18938-60-8 ]

[ 18938-60-8 ] Synthesis Path-Upstream   1~10

  • 1
  • [ 24424-99-5 ]
  • [ 16874-12-7 ]
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YieldReaction ConditionsOperation in experiment
98% With triethylamine In DMF (N,N-dimethyl-formamide); dichloromethane at 20℃; for 2.00 h; To a solution of 9.82 g (0.041 m) of (L)-tyrosine, tert-butyl ester in 150 ml of methylene chloride and 20 ml of DMF was added 5.2 g (0.04 m) of triethyl amine followed by 9.03 g (0.04 m) of ditertbutyldicarbonate. The reaction mixture was stirred for 2 hours at room temperature and was then washed with 1 N HCl (3.x.50 ml), NaHCO3 solution (1.x.50 ml) and brine (1.x.50 ml) and was dried over MgSO4. The mixture was filtered and concentrated in vacuo to give 13.59 g (98percent yield) of a white solid. 300 MHz 1H NMR (CDCl3): 1.42 (s, 18H); 2.95 (d, 2H); 4.39 (dd, 1H); 5.01 (d, 1H); 6.15 (s, 1H); 6.70 (d, 2H); 7.00 d, 2H).
96% With triethylamine In 1,4-dioxane; water at 21℃; Inert atmosphere To a stirred solution of Tyr-OBut (4) (5.0 g, 21.0 mmol) in dioxane and water (42 ml, 0.5 M, dioxane/water = 1/1) were added Et3N (3.27 g, 4.5 mL, 32.3 mmol, 1.54 equiv) and (Boc)2O (5.56 g, 24.4 mmol, 1.14 equiv). The reaction mixture was stirred at rt overnight. After confirming the completion of the reaction by TLC, the reaction mixture was acidified to pH 3 by adding 10percent aqueous KHSO4, and extracted with EtOAc. The organic layers were washed with brine, dried (Na2SO4) and evaporated. Column chromatography on silica gel (petroleum ether/EtOAc = 20/1 then 2/1) to yield N-Boc-Tyr(OH)-OBut (5) (6.82 g, 96percent) as a white solid, mp 106-107°C (lit.12 112.8-113.0 °C (nhexane/CH2Cl2)). The spectroscopic data of compound 5 were identical to those reported in the literature.
95% With sodium hydrogencarbonate In N,N-dimethyl-formamide at 20℃; for 3.00 h; Example 1 (0506) This example details the synthesis of the carbonyl-containing amino acid presented in FIG. 4. The carbonyl-containing non-natural amino acid was produced as described in FIG. 4.
94% With sodium carbonate In water; acetone for 18.00 h; To a stirring solution of sodium bicarbonate (37.4 g, 445 mmol) in water (1 L) was added (S)-tert-b\ity\ 2-amino-3-(4-hydroxyphenyl)propanoate (96 g, 405 mmol) and acetone (850 mL). A solution of di-tert-butyl dicarbonate (97 g, 445 mmol) in acetone (220 mL) was then added slowly over 2 h. After a further 16 h, the mixture was treated with water (1.7 L) then treated with a solution of AcOH (30 mL) in water (300 mL) added slowly. The mixture was extracted with EA (1 L) and the organics dried over Na2SO4 and partially concentrated. The residue was re-slurried with iso- hexanes (1 L). The precipitate was collected by filtration, washing with iso-hexanes (100 mL) to afford 128.4 g (94percent) of tert-butyl (ri-butoxycarbonyl)-L-tyrosinate. LCMS-ESI (m/z) calculated for Ci8H27NO5: 337.2; found 360.2 [M+Na]+, tR = 5.93 min (Method 10).
85% With triethylamine In 1,4-dioxane; water at 20℃; To a solution of commercially available L-tyrosine ieri-butyl ester (700 mg, 2.95 mmol) in 50 mL of Dioxane-H20 (5: 1), NEt3 (1.23 ml, 8.85 mmol) and (Boc)20 (966 mg, 4.42 mmol) were added, and the reaction mixture was stirred at room temperature. When TLC indicated the consumption of L- tyrosine ieri-butyl ester, the reaction mixture was concentrated under reduced pressure to remove dioxane, and then the resulting solution was diluted with water and extracted with EtOAc (2 χ 50 mL). The combined organic layer was washed with brine, dried over Na2S04, filtered, and concentrated under reduced pressure to give the crude product. Purification by flash chromatography on silica gel with MeOH:CH2CI2 (1 :20) afforded the title compound as a white solid (846 mg, 85percent). For more details and analytical data, see: Wang, L; Qu, W.; Lieberman, B. P.; Plossl, K.; Kung, H. F. Nucl. Med. Biol. 201 1, 38, 53-62)
77% With triethylamine In dichloromethane at 0 - 20℃; for 18.00 h; Step 1.
2-Methyl-2-propanyl N-{[(2-methyl-2-propanyl)oxy]carbonyl}-L-tyrosinate
To a solution of L-tyrosine tert-butyl ester (1.43 g, 2.64 mmol) in CH2Cl2 (5.0 mL) was added triethylamine (0.320 mL, 2.31 mmol) and di-tert-butyldicarbonate (0.303 g, 1.39 mmol) at 0° C.
After the solution was stirred at room temperature for 18 h, the solution was diluted with CH2Cl2 and washed with 2 N HCl(aq).
The organic layer was dried over MgSO4(s), filtered, and concentrated.
The residue was purified by Isco Combi-Flash Companion column chromatography (0-30percent ethyl acetate in n-hexane) to give 2-methyl-2-propanyl N-{[(2-methyl-2-propanyl)oxy]carbonyl}-L-tyrosinate (299 mg, 77percent) as a white solid. 1H NMR (CDCl3, 400 MHz) δ 7.02 (d, 2H), 6.73 (d, 2H), 5.59 (br s, 1H), 5.00 (br d, 1H), 4.39 (q, 1H), 3.01-2.92 (m, 2H), 1.42 (s, 9H), 1.41 (s, 9H).

Reference: [1] Patent: US6353099, 2002, B1. Location in patent: Page column 28
[2] Arkivoc, 2014, vol. 2014, # 3, p. 228 - 238
[3] Patent: EP1828224, 2016, B1. Location in patent: Page/Page column 197
[4] Patent: WO2016/15014, 2016, A1. Location in patent: Paragraph 0384
[5] Amino Acids, 2014, vol. 46, # 8, p. 1947 - 1959
[6] Patent: WO2017/68070, 2017, A1. Location in patent: Page/Page column 44
[7] Patent: US2017/253569, 2017, A1. Location in patent: Paragraph 0708-0709
[8] Patent: WO2010/39474, 2010, A1. Location in patent: Page/Page column 9
[9] Organic and Biomolecular Chemistry, 2014, vol. 12, # 26, p. 4708 - 4715
[10] Organic Process Research and Development, 2018, vol. 22, # 2, p. 236 - 240
  • 2
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YieldReaction ConditionsOperation in experiment
88.5% With sodium hydrogencarbonate In water; acetone at 20 - 25℃; for 2.00 h; Large scale A 100L stirred reactor was charged with water (52.5 kg), sodium bicarbonate (4.0 kg, 46.0 moles), L-tyrosine-t-butyl ester HC1 (1) (10.0 kg, 42.2 moles) and acetone (36 kg). The mixture was stirred at 20-25°C. In a separate vessel, di-tert-butyl dicarbonate (10.0 kg, 45.8 moles) and acetone (10 kg) were charged and the mixture stirred until a solution is formed. The Boc2O/acetone solution was charged to the reactor over a period of lh while controlling the addition so that the temperature did not exceed 25°C. The mixture was stirred for 2 h at 20-25°C then sampled for completion by HPLC analysis. Upon completion, the reaction mixture was concentrated under ambient pressure to remove approximately 80percent of volume (40L). The resulting mixture was cooled to 20-25°C. MTBE (37 kg) and acetic acid (2 kg) were charged to the reactor and the mixture stirred for 10-20 minutes after which stirring was stopped and the phasesallowed to separate. The organic layer was collected and the aqueous layer returned to the reactor. MTBE (38 kg) was charged to the reactor and the mixture stirred for 10-20 minutes. Stirring was stopped and the phases allowed to separate. The aqueous layer was drained form the reactor and the first organic extract recharged to the reactor. Water (71 kg) was charged to the reactor and the mixture stirred for 10-20 minutes.Stirring was stopped to allow the phases to separate. The aqueous phase was drained from the reactor. The remaining organic phase was concentrated under ambient pressure to remove approximately 90percent of volume. The mixture was cooled to 0-5°C over a period of 2-3 h. Petroleum ether (32 kg) was added and the mixture stirred for 3h at 0-5°C. The resulting slurry was filtered then dried in an oven under reducedpressure at 3 5-40°C for 16h to obtain N-tert-butoxycarbonyl-L-tyrosine-t-butyl ester (2) (12.6 kg, 37.3 moles, 88.5percent yield, HPLC purity: 99percent).
Reference: [1] Patent: WO2018/64476, 2018, A1. Location in patent: Paragraph 125; 126; 127
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Reference: [1] Chemistry - A European Journal, 2013, vol. 19, # 5, p. 1720 - 1725
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  • [ 75-65-0 ]
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Reference: [1] Nucleosides, Nucleotides and Nucleic Acids, 2001, vol. 20, # 4-7, p. 315 - 321
[2] Journal of Medicinal Chemistry, 2000, vol. 43, # 23, p. 4570 - 4574
[3] Chemistry - An Asian Journal, 2011, vol. 6, # 6, p. 1316 - 1320
  • 5
  • [ 60-18-4 ]
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Reference: [1] Organic and Biomolecular Chemistry, 2014, vol. 12, # 26, p. 4708 - 4715
  • 6
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Reference: [1] Photochemistry and Photobiology, 2015, vol. 91, # 6, p. 1422 - 1428
  • 7
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Reference: [1] Photochemistry and Photobiology, 2015, vol. 91, # 6, p. 1422 - 1428
  • 8
  • [ 98946-18-0 ]
  • [ 3978-80-1 ]
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  • [ 158008-98-1 ]
Reference: [1] Tetrahedron Letters, 1998, vol. 39, # 12, p. 1557 - 1560
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Reference: [1] Journal of Organic Chemistry USSR (English Translation), 1968, vol. 4, p. 942 - 945[2] Zhurnal Organicheskoi Khimii, 1968, vol. 4, p. 971 - 975
  • 10
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Reference: [1] Bioorganic and Medicinal Chemistry Letters, 2002, vol. 12, # 5, p. 729 - 731
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