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Chemical Structure| 220587-29-1

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Product Details of [ 220587-29-1 ]

CAS No. :220587-29-1
Formula : C21H32BNO6
M.W : 405.29
SMILES Code : O=C(OC)[C@@H](NC(OC(C)(C)C)=O)CC1=CC=C(B2OC(C)(C)C(C)(C)O2)C=C1
MDL No. :MFCD16251714

Safety of [ 220587-29-1 ]

GHS Pictogram:
Signal Word:Warning
Hazard Statements:H302-H315-H319-H335
Precautionary Statements:P261-P305+P351+P338

Application In Synthesis of [ 220587-29-1 ]

* 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.

  • Upstream synthesis route of [ 220587-29-1 ]

[ 220587-29-1 ] Synthesis Path-Upstream   1~3

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YieldReaction ConditionsOperation in experiment
76% at 20℃; for 0.5 h; This ester compound 6 was prepared based on a literature procedure (Firooznia, et al, Tetrahedron Lett., 1999, 40, 213-216). Bis(pinacolato)diboron (90 g, 1.1 eq), potassium acetate (63 g, 2 eq), tricyclohexylphosphine (2.3 g, 2.5percent mol), and palladium acetate (0.72 g, 1 molpercent) were mixed in acetonitrile (950 ml) and the resulting mixture stirred at room temperature for 5 minutes. The above triflate (5) solution (190 g, 0.32 mol) was added and the resulting mixture was heated at 800C for 1 hours and cooled. HPLC showed complete consumption of the starting material. The reaction mixture was quenched with aqueous potassium bicarbonate solution (57 g in 475 ml water) and resulting mixture was stirred at room temperature for 30 minutes. The mixture was filtered through a pad of 20 μ cellulose to remove palladium black. A sample of the organic layer was concentrated and purified by column chromatography (gradient: 1 : 10 to 1 :4 ethyl acetate/hexanes) to give the ester compound 6 as a clear oil. LC-MS (ESI): MH+ = 406.2, MNH4+ = 423.2, M2H+ = 811.5, M2NH4+ = 428.5. IH NMR (CDCl3) δ 7.76 (d, J= 8.1 Hz, 2H), 7.15 (d, J= 7.6 Hz, 2H), 4.96 (d, J= 7.3 Hz, IH), 4.60 (m, IH), 3.72 (s, 3H), 3.13 (m, 2H), 1.44 (s, 9H), 1.36 (s, 12H). The above organic layer of 6 was stirred with aqueous lithium hydroxide solution (23 g in 500 ml water) at room temperature for 30 minutes. The pH of the resulting slurry was adjusted to about 10 with 6 N hydrochloric acid and filtered. The cake was washed with water (200 ml). Acetonitrile was removed from the filtrate under reduced pressure to give an aqueous slurry (950 ml, additional water was added during distillation). The slurry was filtered through a pad of 20 μ cellulose and washed with water (200 ml). The filtrate was washed with MTBE (500 ml) and rediluted with 700 ml MTBE. The mixture was acidified to pH about 4.5 with 6 N hydrochloric acid. The organic layer was washed with water (500 ml) and concentrated under reduced pressure to the titled product (7) as a brown oil (206 g, 95percent yield based on estimated purity by NMR). The crude product was used directly in the following step. LC-MS (ESI): MH+ = 392.2, MNH4+ = 409.2, M2H+ = 783.4, M2NH4+ = 800.4. 1H NMR (CDCl3) δ 7.95 (br s, IH), 7.76 (d, J= 7.8 Hz, 2H), 7.21 (d, J= 7.6 Hz, 2H), 5.03 (d, J= 7.8 Hz, IH), 4.62 (m, IH), 3.18 (m, 2H), 1.43 (s, 9H), 1.35 (s, 12H). 13C NMR (CDCl3) δ 175.8, 155.7, 139.7, 135.4, 129.2, 84.2, 80.5, 54.5, 38.3, 28.7, 25.2.Compound 7 can optionally isolated by crystallization. Thus, the above MTBE solution of 7 can be dried with anhydrous Na2SO4 and concentrated to about 1.0 vol under vacuum. Heptane (2.5 vol) was added and concentrated to about 1.5 vol under vacuum. Heptane (4.2 vol) was added slowly at 36~42°C followed by cooling slowly to 5~10°C. The resulting slurry is filtered, washed by heptane, and dried under vacuum at 20-300C to give the product 7 in about 76percent yield.
4.91g With lithium hydroxide In tetrahydrofuran; water at 20℃; for 1 h; (2S) -2- (tert-butoxycarbonylamino) -3- [4- (4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl) phenyl] propionate (5.21 g, a 12.9 mmol) was dissolved in tetrahydrofuran (60 mL), 4N aqueous lithium hydroxide solution (6.45 mL, and stirred for 1 hour at room temperature was added a 25.8 mmol). The reaction was diluted with saturated aqueous sodium chloride solution, and extracted with ethyl acetate. After drying the extract over anhydrous sodium sulfate combined, to give the title compound (4.91 g) under reduced pressure to concentrate.
602 mg With water; lithium hydroxide In tetrahydrofuran; methanol at 20℃; for 5 h; An aqueous solution of LiOH (216 mg, 5.04 mmol, 3 equiv) in H2O (3.30 mL) was added to a solution of Boc-Phe(4-BPin)-OMe (680 mg, 1.68 mmol, 1 equiv) in MeOH/THF (1:1, 6.60 mL).The reaction mixture was stirred at room temperature for 5 h. After this time, the organic solvents were evaporated under reduced pressure and H2O (100 mL) was added to the resulting residue. The resulting solution was adjusted to pH 5 by addition of glacial AcOH followed by extraction with EtOAc (4 × 30 mL). The organic layers were combined, washed with brine (50 mL), and dried over anhydrous magnesium sulfate. Removal of the solvent afforded Boc-Phe(4-BPin)-OH [4] as a white solid (602 mg, 92percent yield). tR = 6.43 min (98percent purity).
References: [1] Patent: WO2010/47712, 2010, A1, . Location in patent: Page/Page column 26-27.
[2] Patent: US2009/48280, 2009, A1, . Location in patent: Page/Page column 9; 12-13.
[3] Patent: US2009/99206, 2009, A1, . Location in patent: Page/Page column 6.
[4] Patent: JP2016/37467, 2016, A, . Location in patent: Paragraph 0063.
[5] Beilstein Journal of Organic Chemistry, 2019, vol. 15, p. 761 - 768.
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YieldReaction ConditionsOperation in experiment
95 %Spectr.
Stage #1: at 20℃; for 0.5 h;
Stage #2: With hydrogenchloride In tert-butyl methyl ether; water
The above organic layer of the ester was stirred with aqueous lithium hydroxide solution (23 g in 500 mL water) at r.t. for 30 minutes. The pH of the resulting slurry was adjusted to about 10 with 6 N hydrochloric acid and filtered. The cake was washed with water (200 mL). Acetonitrile was removed from the filtrate under reduced pressure to give an aqueous slurry (950 mL, additional water was added during distillation). The slurry was filtered through a pad of 20 micron cellulose and washed with water (200 mL). The filtrate was washed with MTBE (500 mL) and rediluted with 700 mL MTBE. The mixture was acidified to pH about 4.5 with 6 N hydrochloric acid. The organic layer was washed with water (500 mL) and concentrated under reduced pressure to the acid compound as a brown oil (206 g, 95percent yield based on estimated purity by NMR). The crude product can be used directly in the following step. Alternatively, the compound can be purified by crystallization from MTBE/heptane to give a white solid, which contains a small amount of the corresponding boronic acid, (S)-3-(4-boronophenyl)-2-(tert-butoxycarbonylamino)propanoic acid. MS (ESI): MH+=392.2, MNH4+=409.2, M2H+=783.4, M2NH4+=800.4. 1H NMR (CDCl3) δ 7.95 (br s, 1H), 7.76 (d, J=7.8 Hz, 2H), 7.21 (d, J=7.6 Hz, 2H), 5.03 (d, J=7.8 Hz, 1H), 4.62 (m, 1H), 3.18 (m, 2H), 1.43 (s, 9H), 1.35 (s, 12H). 13C NMR (CDCl3) δ 175.8, 155.7, 139.7, 135.4, 129.2, 84.2, 80.5, 54.5, 38.3, 28.7, 25.2.
95 %Spectr.
Stage #1: With lithium hydroxide; water In acetonitrile at 20℃; for 0.5 h;
Stage #2: With hydrogenchloride In tert-butyl methyl ether; water
The above organic layer of the ester was stirred with aqueous lithium hydroxide solution (23 g in 500 mL water) at room temperature for 30 minutes. The pH of the resulting slurry was adjusted to about 10 with 6 N hydrochloric acid and filtered. The cake was washed with water (200 mL). Acetonitrile was removed from the filtrate under reduced pressure to give an aqueous slurry (950 mL, additional water was added during distillation). The slurry was filtered through a pad of cellulose and washed with water (200 mL). The filtrate was washed with MTBE (500 mL) and rediluted with 700 mL MTBE. The mixture was acidified to pH about 4.5 with 6 N hydrochloric acid. The organic layer was washed with water (500 mL) and concentrated under reduced pressure to the acid compound as a brown oil (206 g, 95percent yield based on estimated purity by NMR). The crude product can be used directly in the following step. Alternatively, the compound can be purified by crystallization from MTBE/heptane to give a white solid, which contains a small amount of the corresponding boronic acid, (S)-3-(4-boronophenyl)-2-(tert-butoxycarbonylamino)propanoic acid. MS (ESI): MH+=392.2, MNH4+=409.2, M2H+=783.4, M2NH4+=800.4. 1H NMR (CDCl3) δ 7.95 (br s, 1H), 7.76 (d, J=7.8 Hz, 2H), 7.21 (d, J=7.6 Hz, 2H), 5.03 (d, J=7.8 Hz, 1H), 4.62 (m, 1H), 3.18 (m, 2H), 1.43 (s, 9H), 1.35 (s, 12H). 13C NMR (CDCl3) δ 175.8, 155.7, 139.7, 135.4, 129.2, 84.2, 80.5, 54.5, 38.3, 28.7, 25.2.
References: [1] Patent: US2009/62540, 2009, A1, . Location in patent: Page/Page column 8-9.
[2] Patent: US2009/88447, 2009, A1, . Location in patent: Page/Page column 5-6.
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References: [1] Patent: US2011/124865, 2011, A1, . Location in patent: Page/Page column 4; 5.
 

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