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CAS No. :124150-87-4 MDL No. :MFCD01862147
Formula : C9H20O2Si Boiling Point : -
Linear Structure Formula :- InChI Key :YANSSVVGZPNSKD-MRVPVSSYSA-N
M.W : 188.34 Pubchem ID :11008692
Synonyms :

Safety of [ 124150-87-4 ]

Signal Word:Warning Class:N/A
Precautionary Statements:P210-P231+P232-P235-P261-P270-P271-P280-P301+P312-P302+P352-P304+P340-P305+P351+P338-P309+P311-P370+P378-P403+P233-P403+P235 UN#:N/A
Hazard Statements:H227-H302-H315-H319-H335 Packing Group:N/A
GHS Pictogram:

Application In Synthesis of [ 124150-87-4 ]

* 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.

  • Downstream synthetic route of [ 124150-87-4 ]

[ 124150-87-4 ] Synthesis Path-Downstream   1~100

  • 1
  • [ 6089-04-9 ]
  • [ 124150-87-4 ]
  • [ 123151-84-8 ]
YieldReaction ConditionsOperation in experiment
34% With n-butyllithium; N,N,N,N,-tetramethylethylenediamine In tetrahydrofuran at -78℃;
With n-butyllithium; boron trifluoride diethyl etherate In tetrahydrofuran at -78℃; for 2.33333h;
  • 2
  • [ 124150-87-4 ]
  • 6-[1,3]Dithian-2-yl-3,4-dihydro-2H-pyran [ No CAS ]
  • (S)-1-(tert-Butyl-dimethyl-silanyloxy)-3-[2-(5,6-dihydro-4H-pyran-2-yl)-[1,3]dithian-2-yl]-propan-2-ol [ No CAS ]
YieldReaction ConditionsOperation in experiment
90% With n-butyllithium In tetrahydrofuran at -78 - 30℃; for 1h;
  • 3
  • [ 18162-48-6 ]
  • [ 60456-23-7 ]
  • [ 124150-87-4 ]
YieldReaction ConditionsOperation in experiment
99% With 1H-imidazole In dichloromethane
99% With 1H-imidazole In N,N-dimethyl-formamide at 0 - 20℃;
98% With 1H-imidazole In tetrahydrofuran at 20℃; for 18h; Inert atmosphere;
98% With 1H-imidazole In tetrahydrofuran at 20℃; Inert atmosphere;
96% With 1H-imidazole In N,N-dimethyl-formamide at 0℃; for 1h;
96% With 1H-imidazole In tetrahydrofuran at 20℃; for 2h; Inert atmosphere; Schlenk technique;
95% With 1H-imidazole In tetrahydrofuran; N,N-dimethyl-formamide at 0 - 20℃;
95% With 1H-imidazole In dichloromethane at 0 - 20℃; for 6h; To a solution of (5)-glycidol S6 (6.70 g, 90.0 mmol; AK Scientific) in dichloromethane (250 mL) was added imidazole (7.40 g, 108 mmol) and TBSC1 (14.9 g, 99.0 mmol) at 0 °C. The reaction was stirred for 6 hr at room temperature before quenched with water (200 mL), and the resulting two layers were separated. The organic layer was dried over anhydrous Na2S04, and filtered, concentrated under reduced pressure to give a crude oil. Purification over S1O2 (hexanes/ethyl acetate = 50/1) gave S7 as a clear oil (16.2 g, 95%). S7: [GC]D = -2.2 (C 1.0, CHC13); 1H MR (500 MHz, CDC13) δ: 3.85 (1H, dd, J= 9.6, 3.2 Hz), 3.66 (1H, dd, J= 11.9, 5.0 Hz), 3.09 (1H, ddd, J= 7.5, 4.4, 3.0 Hz), 2.77 (1H, dd, J= 5.1, 4.5 Hz), 2.64 (1H, dd, J = 5.2, 2.6 Hz), 0.9 (9H, s), 0.09 (3H, s), 0.08 (3H, s) ppm. 13C NMR (125 MHz, CDC13) δ: 63.7, 52.4, 44.4, 25.8, 18.3, -5.3, -5.4 ppm. HRMS (ESI) m/z: [M+H]+ calcd for C9H21O2S1 189.1305; found 189.1299.
92% Stage #1: (S)-oxiranemethanol With 1H-imidazole; dmap In dichloromethane at 0℃; for 0.25h; Stage #2: tert-butyldimethylsilyl chloride In dichloromethane at 0 - 20℃; for 1.41667h; 4 Example 4. Synthesis of Aldehyde Building Block 418.413 95% 414 62% 415OTBSTBSOTf, 2,6-lutidine TMS OTBS CSA S-A. ^OTBSCH2Cl2 ^^ CH 2C12, CH3OH91% 416 41767%DMSO, (COCl)2 TMS^ OTBSEt3N, CH2Cl2 418 CHOSynthesis of Compound 414. To a solution of commercially available (S)- glycidol (413, 5.10 g, 68.8 mmol) in methylene chloride (40 mL) at 0 0C was added imidazole (6.10 g, 89.5 mmol), followed by 4-dimethylaminopyridine (0.420 g, 3.40 mmol), and then stirred at 0 0C for 15 min. A solution of tert- butylchlorodimethylsilane (10.4 g, 68.8 mmol) in dry methylene chloride (20 mL) was then added dropwise over 5 min. The reaction was stirred at 0 0C for 20 min and then at room temperature for 1 h. After this time, the mixture was quenched with water (100 mL), diluted with diethyl ether (300 mL) and the layers were separated. The aqueous layer was extracted with diethyl ether (2 x 200 mL) and the combined organic layers were dried over magnesium sulfate, filtered and concentrated. Purification by flash chromatography (silica plug, hexanes to 95:5 hexanes/ethyl acetate) afforded 414 (11.8 g, 92%) as a light yellow oil.
92% With 1H-imidazole In dichloromethane at 0 - 20℃; for 1.41667h; 1 Synthesis of Compound 414. To a solution of commercially available (S)- glycidol (413, 5.10 g, 68.8 mmol) in methylene chloride (40 mL) at 0 0C was added imidazole (6.10 g, 89.5 mmol), followed by 4-dimethylaminopyridine (0.420 g, 3.40 mmol), and then stirred at 0 0C for 15 min. A solution of tert- butylchlorodimethylsilane (10.4 g, 68.8 mmol) in dry methylene chloride (20 mL) was then added dropwise over 5 min. The reaction was stirred at 0 0C for 20 min and then at room temperature for 1 h. After this time, the mixture was quenched with water (100 mL), diluted with diethyl ether (300 mL) and the layers were separated. The aqueous layer was extracted with diethyl ether (2 x 200 mL) and the combined organic layers were dried over magnesium sulfate, filtered and concentrated. Purification by flash chromatography (silica plug, hexanes to 95:5 hexanes/ethyl acetate) afforded 414 (11.8 g, 92%) as a light yellow oil.
91% With 1H-imidazole In dichloromethane at -10 - 20℃; for 6h;
91% With 1H-imidazole In tetrahydrofuran at 20℃; Inert atmosphere;
91% With dmap; triethylamine In dichloromethane at 0 - 20℃; for 5h; Inert atmosphere;
90% With dmap; triethylamine In dichloromethane
86% With 1H-imidazole In dichloromethane at 0 - 10℃; Inert atmosphere; 4.3 Synthesis of Compound 2012: A three-neck, 22-L, round-bottom flask equipped with a magnetic stirrer, a temperature probe, and an addition funnel with a nitrogen inlet was charged with (5)-(-)-glycidol (1.0 kg, 13.5 mol) and DCM (3.0 L). Imidazole (1.01 kg, 14.8 mol) and DMAP (84 g, 680 mmol) were added and the reaction was cooled to 0 0C. A solution of TBDMSCl (2.04 kg, 13.5 mol) in DCM (2.0 L) was added while maintaining the internal temperature below 10 0C. The reaction was stirred at 0 0C for 2 h and analyzed by TLC (9:1 heptane/EtOAc) which indicated that the reaction was complete. The reaction mixture was purified by silica- gel plug in two bathes (silica gel: 6 kg each) using DCM as eluent to afford the desired product as a colorless oil (2.2 kg, 86% yield). The 1H NMR spectrum was consistent with the assigned structure of compound 2012.
79% With triethylamine In dichloromethane 30.C (S)-1-(1-{2-Hydroxy-3-[5-methanesulfonyl-3-(4-trifluoromethyl-phenyl)-4,5,6,7-tetrahydro-pyrazolo[4,3-c]pyridin-1-yl]-propyl}-piperidin-4-yl)-3-methyl-1,3-dihydro-benzoimidazol-2-one C. (R)-tert-Butyl-dimethyl-oxiranylmethoxy-silane. tert-Butyl-chloro-dimethylsilane (12.9 g, 85.5 mmol) followed by Et3N (19 mL, 136 mmol) was added to a 0° C. solution of (S)-(+)-glycidol (5.0 g, 67 mmol) in CH2Cl2 (200 mL). The solution was allowed to warm to 23° C. with stirring over 17 h. The resulting pink solution was diluted with Et2O (800 mL) and stirred an additional 30 min. The Et2O layer was washed with saturated aqueous NaHCO3 (200 mL), H2O (2*100 mL), brine (100 mL), dried over Na2SO4 and concentrated. Purification by column chromatography (silica, 5-10% Et2O/hexanes) gave (R)-tert-Butyl-dimethyl-oxiranylmethoxy-silane (10.01 g, 79%). TLC (silica, 10% Et2O/hexanes): Rf=0.5. 1H NMR (CDCl3, 400 MHz): 3.85 (dd, J=11.9, 3.2 Hz, 1H), 3.66 (dd, J=11.9, 4.8 Hz, 1H), 3.09 (m, 1H), 2.77 (dd, J=5.0, 4.2 Hz, 1H), 2.64 (dd, J=5.2, 2.7 Hz, 1H), 0.90 (s, 9H), 0.08 (s, 3H), 0.07 (s, 3H).
75% With dmap; triethylamine In dichloromethane at 20℃; for 5h;
72% With 1H-imidazole In tetrahydrofuran at 20℃; for 1h; Inert atmosphere;
60% With 1H-imidazole In N,N-dimethyl-formamide at 0℃;
With 1H-imidazole
With 1H-imidazole; dmap In dichloromethane at 0℃; for 2h; Synthesis of (R)-2-(tert-butyldiphenylsilyloxy)-5-(trimethylsilyl)pent-4-yn-1-ol (6): A solution of (S)-glycidol (4, 50.0 g, 0.675 mol), imidazole (57.5 g, 0.844 mol), and 4-dimethylaminopyridine (4.7 g, 0.038 mol) in anhydrous dichloromethane (150 mL) was cooled to 0 °C and a solution of tert-butylchlorodimethylsilane (115.3 g, 0.762 mol) in dichloromethane (100 mL) was added. The reaction was stirred at 0 °C for 2 h. After this time, the reaction was diluted with dichloromethane (100 mL), filtered through a silica gel plug and the plug washed with dichloromethane (3 liter). The pure fractions (as determined by TLC analysis) were combined and concentrated to afford epoxide 4a as a colorless oil.
With 1H-imidazole; dmap In dichloromethane at 10℃; for 0.5h;
With 1H-imidazole In N,N-dimethyl-formamide at 0℃; for 0.5h; Inert atmosphere; 3 Example 3: (/f)-tert-butyldimethyl(oxiran-2-ylmethoxy)silane (2a). Example 3: (/f)-tert-butyldimethyl(oxiran-2-ylmethoxy)silane (2a). TBSCI O imidazole o ^^0H DMF, 0 °C* ^^OTBS 1 2a 100% ee [0343] To a 0 °C solution of ieri-butyl(chloro)dimethylsilane (26.540 g, 176.21 mmol, 1.3 equiv) and imidazole (14.786 g, 217.19 mmol, 1.6 equiv) in dimethylformamide (80mL) was added (S)- oxiran-2-yl methanol (10.013 g, 135.16 mmol, 1.0 equiv) drop-wise and the resulting mixture stirred at that temperature under nitrogen for 30 minutes. The reaction was then quenched with addition of saturated aqueous ammonium chloride (200 mL) and water (200 mL). The resulting mixture was extracted with heptane (5 x 200 mL) and the combined organic phases were washed with brine, dried (MgS04) and concentrated to give 25.142 g (99%) of the title compound as a yellow oil. This material was used in the next step without purification. Data for 2a: Rf = 0.64 (20% EtOAc / heptane); *H NMR (400 MHz, CDC13) δ 3.85 (dd, 7=3.22, 12.01 Hz, 1H), 3.66 (dd, 7=4.69, 12.01 Hz, 1H), 3.05-3.12 (m, 1H), 2.76 (dd, 7=4.25, 5.13 Hz, 1H), 2.63 (dd, 7=2.64, 4.98 Hz, 1H), 0.90 (s, 9H), 0.08 (s, 3H), 0.07 (s, 3H).
With 1H-imidazole In N,N-dimethyl-formamide at 0℃; for 0.5h; Inert atmosphere; 3 Example 3: (R)-tert-butyldimethyl(oxiran-2-ylmethoxy)silane (2a). [0324] To a 0 °C solution of ter/-butyl(chloro)dimethylsilane (26.540 g, 176.21 mmol, 1.3 equiv) and imidazole (14.786 g, 217.19 mmol, 1.6 equiv) in dimethylformamide (80mL) was added (S)-oxiran-2-yl methanol (10.013 g, 135.16 mmol, 1.0 equiv) drop-wise and the resulting mixture stirred at that temperature under nitrogen for 30 minutes. The reaction was then quenched with addition of saturated aqueous ammonium chloride (200 mL) and water (200 mL). The resulting mixture was extracted with heptane (5 * 200 mL) and the combined organic phases were washed with brine, dried (MgS04) and concentrated to give 25.142 g (99%) of the title compound as a yellow oil. This material was used in the next step without purification. Data for 2a: Rf = 0.64 (20% EtOAc / heptane); NMR (400 MHz, CDC13) δ 3.85 (dd, J=3.22, 12.01 Hz, 1H), 3.66 (dd, J=4.69, 12.01 Hz, 1H), 3.05-3.12 (m, 1H), 2.76 (dd, J=4.25, 5.13 Hz, 1H), 2.63 (dd, J=2.64, 4.98 Hz, 1H), 0.90 (s, 9H), 0.08 (s, 3H), 0.07 (s, 3H).
7.3 g With 1H-imidazole In dichloromethane at 20℃; for 1h;
With 1H-imidazole In dichloromethane; N,N-dimethyl-formamide at 0℃; A tert-butyl(dimethyl)[(2R)-oxiran-2-ylmethoxylsilane (A-1) tert-butyl(dimethyl)[(2R)-oxiran-2-ylmethoxylsilane (A-1) A solution of (S)-glycidol (2.5 g, 33.7 mmol) in 100 mL of 1:1 DCM/DMF was cooled to 0°C and treated with TBDMS-Cl (6.10 g, 40.5mmol) and imidazole (3.45 g, 50.6 mmol). The mixture was stirred overnight at 0°C. Solution was diluted with DCM and washed with saturated aqueous NaHCO3 and brine, dried over Na2SO4 and concentrated to provide A-1 as a colorless oil. Data for A-1: LRMS mlz (M + H) = 189.21 found; 189.34 required
With 1H-imidazole In dichloromethane at 0 - 20℃; for 6h;

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[8]Current Patent Assignee: HARVARD UNIVERSITY; EISAI CO LTD - WO2019/10363, 2019, A1 Location in patent: Paragraph 00795
[9]Current Patent Assignee: RESOLVYX PHARMACEUTICALS, INC. - WO2010/39531, 2010, A1 Location in patent: Page/Page column 110
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  • 4
  • [ 505-23-7 ]
  • [ 124150-87-4 ]
  • [ 204448-59-9 ]
YieldReaction ConditionsOperation in experiment
83% With 1,3-dimethyl-3,4,5,6-tetrahydro-2(1H)-pyrimidinone; n-butyllithium In tetrahydrofuran 1.) -20 deg C, 2.) -78 to -20 deg C;
  • 5
  • [ 557-93-7 ]
  • [ 124150-87-4 ]
  • [ 204448-23-7 ]
YieldReaction ConditionsOperation in experiment
With copper(l) iodide; tert.-butyl lithium 1.) Et2O, -78 deg C, 2.) -78 to 0 deg C; Yield given. Multistep reaction;
  • 6
  • [ 95452-06-5 ]
  • [ 14618-80-5 ]
  • [ 124150-87-4 ]
  • (R)-1-{2-[(R)-3-Benzyloxy-2-(tert-butyl-dimethyl-silanyloxy)-propyl]-[1,3]dithian-2-yl}-3-(tert-butyl-dimethyl-silanyloxy)-propan-2-ol [ No CAS ]
YieldReaction ConditionsOperation in experiment
56% Stage #1: tert-butyl(1,3-dithian-2-yl)dimethylsilane With tert.-butyl lithium In diethyl ether; pentane at -78 - -45℃; for 1h; Stage #2: (R)-benzyl glycidol In diethyl ether; pentane at -78 - -25℃; for 1h; Stage #3: tert-butyldimethylsilyl (R)-glycidyl ether With N,N,N,N,N,N-hexamethylphosphoric triamide In diethyl ether; pentane at -78 - 20℃; for 2h;
With tert.-butyl lithium 1) Et2O, -78 --> -45 deg C, 1 h; 2) Et2O, -78 --> -25 deg C, 1 h; 3) Et2O, HMPA, -78 --> 0 deg C, 1 h, 0 deg C --> rt, 1 h; Yield given. Multistep reaction;
  • 7
  • [ 40899-71-6 ]
  • [ 124150-87-4 ]
  • [ 252191-34-7 ]
YieldReaction ConditionsOperation in experiment
48% Stage #1: 1-benzenesulfonylindole With n-butyllithium In tetrahydrofuran; hexane at -78 - 5℃; for 2.5h; Stage #2: tert-butyldimethylsilyl (R)-glycidyl ether In tetrahydrofuran; hexane at -78 - 25℃;
  • 8
  • [ 124150-87-4 ]
  • [ 1066-54-2 ]
  • [ 380909-90-0 ]
YieldReaction ConditionsOperation in experiment
99% Stage #1: trimethylsilylacetylene With tert.-butyl lithium Stage #2: tert-butyldimethylsilyl (R)-glycidyl ether With boron trifluoride diethyl etherate Further stages.;
99% Stage #1: trimethylsilylacetylene With tert.-butyl lithium In tetrahydrofuran; pentane at -78℃; for 0.5h; Stage #2: tert-butyldimethylsilyl (R)-glycidyl ether With boron trifluoride diethyl etherate In tetrahydrofuran; pentane at -78 - 20℃; for 3h; Further stages.;
94% Stage #1: trimethylsilylacetylene With n-butyllithium In tetrahydrofuran; hexane at -78℃; for 0.5h; Stage #2: tert-butyldimethylsilyl (R)-glycidyl ether With boron trifluoride diethyl etherate In tetrahydrofuran; hexane at -78℃; for 0.333333h;
90% Stage #1: trimethylsilylacetylene With n-butyllithium In tetrahydrofuran at -78℃; for 0.5h; Inert atmosphere; Stage #2: tert-butyldimethylsilyl (R)-glycidyl ether With boron trifluoride diethyl etherate In tetrahydrofuran at -78℃; for 1h; Inert atmosphere;
90% With n-butyllithium; boron trifluoride diethyl etherate In tetrahydrofuran; hexane at -78℃; for 1h; Inert atmosphere; A solution of trimethylsilyl acetylene (23.8 mL, 167 mmol; Oakwood) in dry THF (76.0 mL) was cooled to -78 °C under Ar atmosphere and treated with -BuLi (2.50 M in hexane, 61.3 mL, 159 mmol). After 30 min, BF3OEt2 (18.9 mL, 159 mmol) was added dropwise followed by slow addition of a solution of epoxide S7 (15.0 g, 79.7 mmol) in THF (30.0 mL) at -78 °C. The reaction mixture was stirred for 1 h at the same temperature before addition of sat '3); 1H MR (500 MHz, CDC13): 5 3.82-3.78 (1H, m), 3.73 (1H, dd, J = 10.0, 4.5 Hz), 3.67 (1H, dd, J = 9.5, 5.5 Hz), 2.52-2.44 (2H, m), 0.92 (9H, s), 0.16 (9H, s), 0.10 (6H, s) ppm. 13C MR (125 MHz, CDC13): δ 102.8, 87.0, 70.1, 65.4, 25.9, 24.5, 18.3, 0.02, -5.4, -5.4 ppm. HRMS (ESI) m/z: [M+Na]+ calcd for Ci4H3oNa02Si2 309.1677; found 309.1677.
90% With n-butyllithium; boron trifluoride diethyl etherate In tetrahydrofuran at -78℃;
84% Stage #1: trimethylsilylacetylene With n-butyllithium In tetrahydrofuran at -78℃; for 0.666667h; Inert atmosphere; Stage #2: tert-butyldimethylsilyl (R)-glycidyl ether With boron trifluoride diethyl etherate In tetrahydrofuran at -78 - 20℃; for 1.5h; Inert atmosphere; 4 Synthesis of Compound 415. To a stirred solution of trimethylsilylacetylene (4.17 g, 42.5 mmol) in tetrahydrofuran (76 mL) at -78 0C under nitrogen was added a solution of w-butyl lithium in tetrahydrofuran (1.41 M, 15.0 mL, 21.2 mmol) over 10 min. The reaction was stirred at -78 0C for 30 min then a solution of 414 (4.00 g, 21.2 mmol) in tetrahydrofuran (15 niL) was then added, followed by boron trifluoride diethyl etherate (3.10 g, 21.2 mmol). The mixture was then stirred at -78 0C for 30 min and then at room temperature for 1 h. After this time the reaction was quenched by adding a saturated aqueous ammonium chloride solution (40 mL) then diluted with diethyl ether (400 mL). The organic layer was separated, washed with brine (250 mL) and concentrated. Purification by flash chromatography (silica, hexanes to 22:3 hexanes/ethyl acetate) afforded 415 (5.13 g, 84%) as a colorless oil.
84% Stage #1: trimethylsilylacetylene With n-butyllithium In tetrahydrofuran at -78℃; for 0.666667h; Inert atmosphere; Stage #2: tert-butyldimethylsilyl (R)-glycidyl ether With boron trifluoride diethyl etherate In tetrahydrofuran at -78 - 20℃; for 1.5h; Inert atmosphere; Stage #3: With water; ammonium chloride In tetrahydrofuran 1 Synthesis of Compound 415. To a stirred solution of trimethylsilylacetylene (4.17 g, 42.5 mmol) in tetrahydrofuran (76 mL) at -78 0C under nitrogen was added a solution of w-butyl lithium in tetrahydrofuran (1.41 M, 15.0 mL, 21.2 mmol) over 10 min. The reaction was stirred at -78 0C for 30 min then a solution of 414 (4.00 g,21.2 mmol) in tetrahydrofuran (15 mL) was then added, followed by boron trifluoride diethyl etherate (3.10 g, 21.2 mmol). The mixture was then stirred at -78 0C for 30 min and then at room temperature for 1 h. After this time the reaction was quenched by adding a saturated aqueous ammonium chloride solution (40 mL) then diluted with diethyl ether (400 mL). The organic layer was separated, washed with brine (250 mL) and concentrated. Purification by flash chromatography (silica, hexanes to 22:3 hexanes/ethyl acetate) afforded 415 (5.13 g, 84%) as a colorless oil.
73% Stage #1: trimethylsilylacetylene With n-butyllithium In tetrahydrofuran at -78℃; for 0.25h; Inert atmosphere; Stage #2: tert-butyldimethylsilyl (R)-glycidyl ether With boron trifluoride diethyl etherate In tetrahydrofuran at -78℃; for 3h; Inert atmosphere;
73% Stage #1: trimethylsilylacetylene With n-butyllithium In tetrahydrofuran at -78℃; for 0.25h; Stage #2: tert-butyldimethylsilyl (R)-glycidyl ether With boron trifluoride diethyl etherate In tetrahydrofuran at -78℃; for 3h; 3; 1 (R)-l, 2-di-(i-Butyldimethylsilyloxy)-5-trimethylsilyl-pent-4-yne (20). (R)-l, 2-di-(i-Butyldimethylsilyloxy)-5-trimethylsilyl-pent-4-yne (20). Part 1: To a solution of TMS acetylene (5.6 mL, 39.8 mmol) in THF (40 mL) was added 2.5 M 7 -BuLi (15.9 mL, 39.8 mmol) at -78°C. After 0.25 h BF3.Et20 (5.0 mL, 39.8 mmol) was added drop wise at -78°C. To the reaction mixture was added (jR)-O-i-butyldimethylsilyl glycidol 13 (5.0 g, 26.5 mmol) and stirred for 3 h at - 78°C. The reaction mixture was warmed to room temperature, quenched with saturated aqueous NH4CI (45 mL) and extracted with Et20 (3 x 45 mL). The organic layer was dried with MgS04, filtered and the solvent removed in vacuo. The crude reaction mixture was purified on silica gel using EtOAc- hexanes (4%) as the eluent to afford 2R, 1, (i-butyldimethyl-silyloxy)-5- trimethylsilyl-pent-4-yn-2-ol (5.5 g, 73%) as a clear colorless oil. XH NMR (400 MHz, CDCls) δ 3.78 (dt, J = 11.1, 5.9 Hz, 1H), 3.72 (dd, J = 10.0, 4.1 Hz, 1H), 3.63 (dd, J = 10.0, 5.6 Hz, 1H), 2.51 - 2.41 (m, 2H), 1.64 (s, lH), 0.91 (s, 11H), 0.14 (s, 2H), 0.09 (s, 5H), 0.08 (s, 6H). C NMR (400 MHz, CDCls) δ 102.96, 87.19, 70.32, 65.60, 26.03, 24.67, 18.48, 0.17, -5.24, -5.28. Part 2: To a solution of the product of Part 1 (5.7g, 19.9 mmol) in anhydrous CH2CI2 (30 mL) was added TBS-C1 (3.6 g, 23.9 mmol), imidazole (1.6g, 23.9 mmol), and DMAP (243 mg, 1.99 mmol) at 0°C. The reaction was allowed to stir at room temperature overnight. It was then quenched with saturated aqueous NH4CI (30 mL) and extracted with EtzO (3 x 30 mL). The combined extract was dried with MgSO4, filtered and evaporated to give a crude clear oil which was then chromatographed on silica gel using EtOAc-hexanes mixture of (1:24) as the eluent to afford the product 20 as a viscous and colorless oil (7.5g, 94%). NMR (400 MHz, CDCls) δ 3.86 - 3.75 (m, lH), 3.60 - 3.47 (m, 2H), 2.50 (dd, J = 16.8, 5.3 Hz, 1H), 2.30 (dd, J = 16.8, 6.5 Hz, 1H), 0.89 (s, 18H), 0.14 (s, 9H), 0.11 (s, 3H), 0.08 (s, 3H), 0.05 (s, 3H), 0.02 (s, 3H). C NMR (400 MHz, CDCls) δ 104.86, 85.95, 72.25, 66.83, 26.13, 26.01, 18.53, 18.29, 0.23, -2.78, -4.29, -4.44, -5.18, -5.24.
Stage #1: trimethylsilylacetylene With n-hexyllithium In tetrahydrofuran; hexane Inert atmosphere; Stage #2: tert-butyldimethylsilyl (R)-glycidyl ether With boron trifluoride diethyl etherate In tetrahydrofuran; hexane at -55℃; 4.3 Synthesis of Compound 2013: A multiple-neck, 72-L, round-bottom flask equipped with a mechanical stirrer, a temperature probe, and an addition funnel with a nitrogen inlet was charged with THF (5.5 L). w-Hexyl lithium (2.3 M in hexane, 5.3 L, 12.3 mol) was added while maintaining the internal temperature below 30 0C. The solution was cooled to -20 0C and TMS acetylene (1.98 L, 1.2 equiv) was added at 0C. The reaction was stirred at 0C for 1 h and a solution of compound 2012 (2.2 kg, 11.66 mol) was added over 75 min at 0C, followed by the addition Of BF3-Et2O (1.44 L, 1.0 equiv) over 110 min at 0C. The reaction was stirred at 0C for 16 h and TLC analysis (9:1 heptane/EtOAc) indicated that the reaction was complete. It was quenched with 75% saturated brine solution (11 L, 5 vol) and diluted with MTBE (11 L, 5 vol). The organic layer was concentrated to dryness to afford a colorless oil (3.43 kg, >;100% yield). The 1H NMR spectrum was consistent with the assigned structure of compound 2013.
Stage #1: trimethylsilylacetylene With tert.-butyl lithium In tetrahydrofuran at -78℃; for 0.5h; Stage #2: tert-butyldimethylsilyl (R)-glycidyl ether With boron trifluoride diethyl etherate In tetrahydrofuran at -78℃; for 4.5h; 1.A STEP A: (R)-I -(tert-butyldimethylsilyloxy)-5-(trimethylsilyl)pent-4-yn-2-ol[0057] tert-BuLi (12.4 ml, 1.7M, 21.1 mmol) was added to a solution of TMS-acetylene (2.12 g, 21.7 mmol) in THF (40 ml) at -78°C and the reaction mixture was stirred for an additional 30 min. (R)-tert- butyldimethyl(oxiran-2-ylmethoxy)silane (2 g, 10.6 mmol) and BF3-EtO2 (3g, 21.1 mmol) were added and stirred at -78°C for 4.5 hours. The reaction was then quenched by addition of aqueous ammonium chloride solution and the mixture was extracted with ethyl acetate (3 x 50 mL). The combined organic layers were washed with brine, dried (MgSO4) and concentrated under reduced pressure to afford the desired material in a quantitative yield. The material was used in the next step with no further purification.
Stage #1: trimethylsilylacetylene With n-butyllithium In tetrahydrofuran; hexane at -70 - -50℃; for 1h; Stage #2: tert-butyldimethylsilyl (R)-glycidyl ether With boron trifluoride diethyl etherate In tetrahydrofuran; hexane at -50℃; for 2h; Synthesis of (R)-2-(tert-butyldiphenylsilyloxy)-5-(trimethylsilyl)pent-4-yn-1-ol (6): To a solution of n-butyl lithium (2.5 M in hexanes, 248 mL, 0.622 mol) in tetrahydrofuran (100 mL) at -70 °C was added trimethylacetylene (101 mL, 70.4 g, 0.717 mol) dropwise via an addition funnel while maintaining the internal temperature below -50 °C. The resulting mixture was stirred at -50 °C for 1 h. At this time, crude epoxide 4a was added dropwise followed by trifluoroborane diethyl etherate (75 mL, 84.8 g, 0.598 mol). The reaction mixture was stirred at -50 °C for 2 h and then was diluted with heptanes (500 mL) and quenched with a saturated aqueous ammonium chloride solution (250 mL) and water (250 mL). The organic layer was separated and concentrated to give crude 5 as pale yellow oil.

Reference: [1]Smith III; Verhoest; Minbiole; Schelhaas [Journal of the American Chemical Society, 2001, vol. 123, # 20, p. 4834 - 4836]
[2]Smith III; Minbiole; Verhoest; Schelhaas [Journal of the American Chemical Society, 2001, vol. 123, # 44, p. 10942 - 10953]
[3]Wang, Bo; Hansen, T. Matthew; Wang, Ting; Wu, Dimao; Weyer, Lynn; Ying, Lu; Engler, Mary M.; Sanville, Melissa; Leitheiser, Christopher; Christmann, Mathias; Lu, Yingtao; Chen, Jiehao; Zunker, Nicholas; Cink, Russell D.; Ahmed, Feryan; Lee, Chi-Sing; Forsyth, Craig J. [Journal of the American Chemical Society, 2011, vol. 133, # 5, p. 1484 - 1505]
[4]Yahata, Kenzo; Ye, Ning; Iso, Kentaro; Ai, Yanran; Lee, Jihoon; Kishi, Yoshito [Journal of Organic Chemistry, 2017, vol. 82, # 17, p. 8808 - 8830]
[5]Current Patent Assignee: HARVARD UNIVERSITY; EISAI CO LTD - WO2019/10363, 2019, A1 Location in patent: Paragraph 00796
[6]Rodriguez, Ana R.; Spur, Bernd W. [Tetrahedron Letters, 2020, vol. 61, # 6]
[7]Current Patent Assignee: RESOLVYX PHARMACEUTICALS, INC. - WO2010/39531, 2010, A1 Location in patent: Page/Page column 110-111
[8]Current Patent Assignee: RESOLVYX PHARMACEUTICALS, INC. - WO2010/91226, 2010, A1 Location in patent: Page/Page column 117-118
[9]Winkler, Jeremy W.; Uddin, Jasim; Serhan, Charles N.; Petasis, Nicos A. [Organic Letters, 2013, vol. 15, # 7, p. 1424 - 1427]
[10]Current Patent Assignee: UNIVERSITY OF SOUTHERN CALIFORNIA - WO2014/130894, 2014, A1 Location in patent: Page/Page column 9; 45; 46
[11]Current Patent Assignee: ANIDA PHARMA - WO2010/120719, 2010, A1 Location in patent: Page/Page column 194; 198-199
[12]Current Patent Assignee: ASTRAZENECA PLC - WO2011/9541, 2011, A1 Location in patent: Page/Page column 22
[13]Allard, Melissa; Barnes, Keith; Chen, Xuemei; Cheung, Yiu-Yin; Duffy, Bryan; Heap, Charles; Inthavongsay, John; Johnson, Matthew; Krishnamoorthy, Ravi; Manley, Chris; Steffke, Stephan; Varughese, Deepu; Wang, Ruifang; Wang, Yi; Schwartz [Tetrahedron Letters, 2011, vol. 52, # 21, p. 2623 - 2626]
  • 9
  • tert-butyldimethylsilyl glycidyl ether [ No CAS ]
  • tert-butyldimethylsilyl (S)-glycidyl ether [ No CAS ]
  • [ 63121-18-6 ]
  • [ 124150-87-4 ]
YieldReaction ConditionsOperation in experiment
42% With (1R,2R)-(-)-N,N'-bis(3,5-di-tert-butylsalicydene)-1,2-cyclohexanediaminocobalt(II); air; acetic acid In tetrahydrofuran at 0 - 20℃;
  • 10
  • tert-butyldimethylsilyl glycidyl ether [ No CAS ]
  • tert-butyldimethylsilyl (S)-glycidyl ether [ No CAS ]
  • [ 124150-87-4 ]
  • (S)-3-((tert-butyldimethylsilyl)oxy)propane-1,2-diol [ No CAS ]
YieldReaction ConditionsOperation in experiment
42% With [(S,S)-N,N’-bis(3,5-di-tertbutylsalicylidene)-1,2-cyclohexanediaminato(2-)]cobalt(II); air; acetic acid In tetrahydrofuran at 0 - 20℃;
  • 11
  • tert-butyldimethylsilyl glycidyl ether [ No CAS ]
  • [ 63121-18-6 ]
  • [ 124150-87-4 ]
  • (S)-3-((tert-butyldimethylsilyl)oxy)propane-1,2-diol [ No CAS ]
YieldReaction ConditionsOperation in experiment
47% With [(S,S)-N,N’-bis(3,5-di-tertbutylsalicylidene)-1,2-cyclohexanediaminato(2-)]cobalt(II); air; acetic acid In tetrahydrofuran at 0 - 20℃;
  • 12
  • [ 4039-83-2 ]
  • [ 124150-87-4 ]
  • [ 808771-39-3 ]
YieldReaction ConditionsOperation in experiment
76% Stage #1: 3-(4-methoxybenzyloxy)propyne With n-butyllithium In tetrahydrofuran; hexane at -78℃; for 1h; Inert atmosphere; Stage #2: tert-butyldimethylsilyl (R)-glycidyl ether With boron trifluoride diethyl etherate In tetrahydrofuran; hexane at -78℃; for 1h; Inert atmosphere;
75% With n-butyllithium; boron trifluoride diethyl etherate In tetrahydrofuran
64% With n-butyllithium; boron trifluoride diethyl etherate In tetrahydrofuran at -78℃;
  • 13
  • [ 400797-73-1 ]
  • [ 124150-87-4 ]
  • 1-[1-[3-(<i>tert</i>-butyl-dimethyl-silanyloxy)-2-hydroxy-propyl]-3-(4-chloro-3-methyl-phenyl)-1,4,6,7-tetrahydro-pyrazolo[4,3-<i>c</i>]pyridin-5-yl]-ethanone [ No CAS ]
YieldReaction ConditionsOperation in experiment
With caesium carbonate In N,N-dimethyl-formamide at 20℃;
  • 14
  • [ 400797-69-5 ]
  • [ 124150-87-4 ]
  • carbonic acid 3-[5-acetyl-3-(4-trifluoromethyl-phenyl)-4,5,6,7-tetrahydro-pyrazolo[4,3-<i>c</i>]pyridin-1-yl]-2-hydroxy-propyl ester <i>tert</i>-butyl ester [ No CAS ]
YieldReaction ConditionsOperation in experiment
With caesium carbonate In N,N-dimethyl-formamide at 20℃;
  • 15
  • [ 925-90-6 ]
  • [ 124150-87-4 ]
  • [ 867267-90-1 ]
YieldReaction ConditionsOperation in experiment
92% With CuCN In tetrahydrofuran at -15℃; for 0.25h;
  • 16
  • tert-butyldimethylsilyl glycidyl ether [ No CAS ]
  • [ 51-79-6 ]
  • [3-(<i>tert</i>-butyl-dimethyl-silanyloxy)-2-hydroxy-propyl]-carbamic acid ethyl ester [ No CAS ]
  • [ 124150-87-4 ]
YieldReaction ConditionsOperation in experiment
With air; 4-nitro-benzoic acid In various solvent(s) at 20℃; for 36h; Title compound not separated from byproducts;
  • 17
  • [ 1826-67-1 ]
  • [ 124150-87-4 ]
  • [ 604775-01-1 ]
YieldReaction ConditionsOperation in experiment
99% With CuCN In tetrahydrofuran at -20℃;
87% Stage #1: vinyl magnesium bromide With copper(l) iodide In tetrahydrofuran at -30℃; for 0.5h; Stage #2: tert-butyldimethylsilyl (R)-glycidyl ether In tetrahydrofuran at -30℃; for 1.5h;
84% Stage #1: vinyl magnesium bromide With copper(I) bromide dimethylsulfide complex In tetrahydrofuran at -78℃; for 0.166667h; Inert atmosphere; Stage #2: tert-butyldimethylsilyl (R)-glycidyl ether In tetrahydrofuran at -78 - 0℃; for 4h; Inert atmosphere;
With CuCN

  • 18
  • [ 879560-02-8 ]
  • [ 124150-87-4 ]
  • 1-(<i>tert</i>-butyl-dimethyl-silanyloxy)-7-phenyl-hepta-4,6-diyn-2-ol [ No CAS ]
YieldReaction ConditionsOperation in experiment
22% Stage #1: (1,1-dibromobut-1-en-3-yn-2-yl)benzene With n-butyllithium In hexane; toluene at -20 - 0℃; Stage #2: tert-butyldimethylsilyl (R)-glycidyl ether With N,N,N,N,N,N-hexamethylphosphoric triamide In diethyl ether; hexane; toluene at -20 - 20℃;
22% Stage #1: (1,1-dibromobut-1-en-3-yn-2-yl)benzene With n-butyllithium In hexane; toluene at -20 - 0℃; Stage #2: tert-butyldimethylsilyl (R)-glycidyl ether With N,N,N,N,N,N-hexamethylphosphoric triamide In diethyl ether; hexane; toluene at -20 - 20℃; Further stages.;
22% Stage #1: (1,1-dibromobut-1-en-3-yn-2-yl)benzene With n-butyllithium In hexane; toluene at -20 - 0℃; Stage #2: tert-butyldimethylsilyl (R)-glycidyl ether With N,N,N,N,N,N-hexamethylphosphoric triamide In diethyl ether; hexane; toluene at -20 - 20℃; Further stages.;
  • 19
  • tert-butyldimethylsilyl glycidyl ether [ No CAS ]
  • [ 124150-87-4 ]
  • (S)-3-((tert-butyldimethylsilyl)oxy)propane-1,2-diol [ No CAS ]
YieldReaction ConditionsOperation in experiment
47% With [(S,S)-N,N’-bis(3,5-di-tertbutylsalicylidene)-1,2-cyclohexanediaminato(2-)]cobalt(II); air; acetic acid In tetrahydrofuran at 0 - 20℃;
42% With [(S,S)-N,N’-bis(3,5-di-tertbutylsalicylidene)-1,2-cyclohexanediaminato(2-)]cobalt(II); air; acetic acid In tetrahydrofuran at 0 - 20℃;
  • 20
  • [ 124150-87-4 ]
  • [ 1730-25-2 ]
  • [ 900519-19-9 ]
YieldReaction ConditionsOperation in experiment
94% With dilithium tetrachlorocuprate In diethyl ether at -30 - 20℃;
90% Stage #1: allylmagnesium bromide With copper(I) bromide dimethylsulfide complex In tetrahydrofuran at -78℃; for 0.5h; Inert atmosphere; Stage #2: tert-butyldimethylsilyl (R)-glycidyl ether In tetrahydrofuran at -78 - 0℃; for 2h; Inert atmosphere;
90% Stage #1: allylmagnesium bromide With dimethylsulfide In tetrahydrofuran; diethyl ether at -78℃; Inert atmosphere; Stage #2: tert-butyldimethylsilyl (R)-glycidyl ether In tetrahydrofuran; diethyl ether at -78 - 20℃; for 2h; Inert atmosphere;
  • 21
  • [ 915790-24-8 ]
  • [ 124150-87-4 ]
  • [ 915790-25-9 ]
YieldReaction ConditionsOperation in experiment
Stage #1: (S)-(11-bromoundecan-2-yloxy)(tert-butyl)diphenylsilane With 1,1-Dibromoethane; magnesium In tetrahydrofuran for 4h; Heating; Stage #2: tert-butyldimethylsilyl (R)-glycidyl ether With copper(I) bromide dimethylsulfide complex In tetrahydrofuran at -25 - 20℃; for 7h;
  • 22
  • [ 400797-90-2 ]
  • [ 124150-87-4 ]
  • (R)-3-[5-methanesulfonyl-3-(4-trifluoromethyl-phenyl)-4,5,6,7-tetrahydro-pyrazolo[4,3-c]pyridin-1-yl]-propane-1,2-diol [ No CAS ]
YieldReaction ConditionsOperation in experiment
40% With 1,3-benzoxazine-2,4-dione; caesium carbonate In methanol; ethyl acetate; N,N-dimethyl-formamide 30.D (S)-1-(1-{2-Hydroxy-3-[5-methanesulfonyl-3-(4-trifluoromethyl-phenyl)-4,5,6,7-tetrahydro-pyrazolo[4,3-c]pyridin-1-yl]-propyl}-piperidin-4-yl)-3-methyl-1,3-dihydro-benzoimidazol-2-one D. (R)-3-[5-Methanesulfonyl-3-(4-trifluoromethyl-phenyl)-4,5,6,7-tetrahydro-pyrazolo[4,3-c]pyridin-1-yl]-propane-1,2-diol. Cs2CO3 (1.88 g, 5.77 mmol) was added to a solution of (R)-tert-Butyl-dimethyl-oxiranylmethoxy-silane (2.72 g, 14.4 mmol) and 5-methanesulfonyl-3-(4-trifluoromethyl-phenyl)-4,5,6,7-tetrahydro-1H-pyrazolo[4,3-c]pyridine (1.70 g, 4.81 mmol) in DMF (13 mL). The mixture was stirred at room temperature for 5 days, then partitioned between EtOAc (400 mL) and saturated NaHCO3 (100 mL). The EtOAc layer was washed with H2O (3*75 mL) and brine (100 mL), dried over Na2SO4 and concentrated. The residue was dissolved in MeOH (125 mL) and treated with CSA (800 mg). The mixture was stirred for 20 h then concentrated. The residue was re-dissolved in EtOAc (200 mL), washed with saturated NaHCO3 (100 mL), dried over Na2SO4 and concentrated. Purification by column chromatography (silica, 20-60% acetone/CH2Cl2) gave the corresponding diol (0.78 g, 40%). TLC (25% acetone/CH2Cl2): Rf=0.2. MS (electrospray): exact mass calculated for C17H21F3N3O4S, 420.11; m/z found, 420.1 [M+H]+. 1H NMR (CD3OD/CDCl3, 400 MHz): 7.74 and 7.67 (A and B of AA'BB', Jab=8.3 Hz, 4H), 4.52 (s, 2H), 4.23 (dd, J=13.0, 3.0 Hz, 1H), 4.04-4.11 (m, 2H), 3.64 (t, J=5.9 Hz, 2H), 3.52 and 3.57 (A and B of ABX, Jab=11.4, Jax=4.8, Jbx=4.9 Hz, 2H), 2.98 (m, 2H), 2.91 (s, 3H).
  • 23
  • [ 124150-87-4 ]
  • [ 231963-90-9 ]
YieldReaction ConditionsOperation in experiment
Multi-step reaction with 3 steps 1: 99 percent / CuCN / tetrahydrofuran / -20 °C 2: 89 percent / TEA / CH2Cl2 / 0.5 h / 0 °C 3: 96 percent / Grubb's catalyst / CH2Cl2 / 15 h / Heating
  • 24
  • [ 124150-87-4 ]
  • [ 867267-81-0 ]
YieldReaction ConditionsOperation in experiment
Multi-step reaction with 2 steps 1: 92 percent / CuCN / tetrahydrofuran / 0.25 h / -15 °C 2: 58 percent / 2,6-di-tert-butyl-4-methylpyridine / CH2Cl2 / 17 h / 20 °C
  • 25
  • [ 18162-48-6 ]
  • [ 124150-87-4 ]
YieldReaction ConditionsOperation in experiment
Multi-step reaction with 2 steps 1: imidazole / CH2Cl2 2: {(R,R)-1,2-[(N=CH-3,5(t-Bu)2-2-phenoxy]2-cyclohexane}Co(II); p-nitrobenzoic acid; air / various solvent(s) / 36 h / 20 °C
  • 26
  • [ 124150-87-4 ]
  • [ 808771-40-6 ]
YieldReaction ConditionsOperation in experiment
Multi-step reaction with 3 steps 1: 75 percent / BuLi; BF3*OEt2 / tetrahydrofuran 2: 88 percent / 2,6-lutidine / CH2Cl2 3: 93 percent / H2; quinoline / Pd-CaCO3-Pb(OAc)2 / hexane
  • 27
  • [ 124150-87-4 ]
  • [ 380909-91-1 ]
YieldReaction ConditionsOperation in experiment
Multi-step reaction with 2 steps 1.1: t-BuLi / tetrahydrofuran; pentane / 0.5 h / -78 °C 1.2: 99 percent / BF3*OEt2 / tetrahydrofuran; pentane / 3 h / -78 - 20 °C 2.1: 78 percent / 2,6-di-tert-butyl-4-methylpyridine / CH2Cl2 / 120 h
Multi-step reaction with 2 steps 1.1: t-BuLi 1.2: 99 percent / BF3*OEt2 2.1: 78 percent / 2,6-di-tert-butyl-4-methylpyridine
  • 28
  • [ 124150-87-4 ]
  • [ 124067-10-3 ]
YieldReaction ConditionsOperation in experiment
Multi-step reaction with 4 steps 1: 1.) BuLi, BF3*Et2O / 1.) hexane, THF, -78 deg C, 30 min; -78 deg C, 20 min, 2.) hexane, THF, -78 deg C, 2 h 2: 78 percent / Rh2(OAc)4 / benzene / 5 h / Heating 3: 95 percent / Et3N / CH2Cl2 / 18 h / 20 °C 4: 79 percent / MeI / acetonitrile / 72 h / Heating
Multi-step reaction with 4 steps 1: 65 percent / BF3*Et2O 2: 76 percent / Rh2(OAc)4 3: 95 percent / Et3N 4: 70 percent / MeI / acetonitrile
  • 29
  • [ 124150-87-4 ]
  • (E)-(R)-6-(tert-Butyl-dimethyl-silanyloxy)-3-iodo-5-(1-methoxycarbonyl-vinyloxy)-hex-2-enoic acid methyl ester [ No CAS ]
YieldReaction ConditionsOperation in experiment
Multi-step reaction with 5 steps 1: 1.) BuLi, BF3*Et2O / 1.) hexane, THF, -78 deg C, 30 min; -78 deg C, 20 min, 2.) hexane, THF, -78 deg C, 2 h 2: 78 percent / Rh2(OAc)4 / benzene / 5 h / Heating 3: 95 percent / Et3N / CH2Cl2 / 18 h / 20 °C 4: 79 percent / MeI / acetonitrile / 72 h / Heating 5: 1.) Bu3SnLi*CuBr*Me2S, MeOH, 2.) I2 / 1.) THF, hexane, -78 deg C, 3 h, 2.) ether, 20 deg C, 2 h
Multi-step reaction with 5 steps 1: 65 percent / BF3*Et2O 2: 76 percent / Rh2(OAc)4 3: 95 percent / Et3N 4: 70 percent / MeI / acetonitrile 5: 1.) (Bu3Sn)Cu*LiBr*Me2S; 2.) iodine / 1.) tetrahydrofuran, -78 deg C; 2.) Et2O
  • 30
  • [ 124150-87-4 ]
  • [ 124067-08-9 ]
YieldReaction ConditionsOperation in experiment
Multi-step reaction with 2 steps 1: 1.) BuLi, BF3*Et2O / 1.) hexane, THF, -78 deg C, 30 min; -78 deg C, 20 min, 2.) hexane, THF, -78 deg C, 2 h 2: 78 percent / Rh2(OAc)4 / benzene / 5 h / Heating
Multi-step reaction with 2 steps 1: 65 percent / BF3*Et2O 2: 76 percent / Rh2(OAc)4
  • 31
  • [ 124150-87-4 ]
  • [ 124067-09-0 ]
YieldReaction ConditionsOperation in experiment
Multi-step reaction with 3 steps 1: 1.) BuLi, BF3*Et2O / 1.) hexane, THF, -78 deg C, 30 min; -78 deg C, 20 min, 2.) hexane, THF, -78 deg C, 2 h 2: 78 percent / Rh2(OAc)4 / benzene / 5 h / Heating 3: 95 percent / Et3N / CH2Cl2 / 18 h / 20 °C
Multi-step reaction with 3 steps 1: 65 percent / BF3*Et2O 2: 76 percent / Rh2(OAc)4 3: 95 percent / Et3N
  • 32
  • [ 124150-87-4 ]
  • (4S,6R)-6-(tert-Butyl-dimethyl-silanyloxymethyl)-4-iodomethyl-4-methyl-[1,3]dioxan-2-one [ No CAS ]
YieldReaction ConditionsOperation in experiment
Multi-step reaction with 2 steps 1: 1.) tert-BuLi, 2.) CuI / 1.) Et2O, -78 deg C, 2.) -78 to 0 deg C 2: 1.) BuLi, 2.) IBr / 1.) Et2O, -78 deg C; THF, 0-20 deg C, 2.) PhMe, -78 to 0 deg C
  • 33
  • [ 124150-87-4 ]
  • (3S,5R)-6-(tert-butyldimethylsilyloxy)-5-hydroxy-3-(phenylmethyl)-2-hexanone [ No CAS ]
YieldReaction ConditionsOperation in experiment
Multi-step reaction with 2 steps 1: 1.) lithium N,N-diisopropylamide, lithium chloride, 2.) (R)-(+)-tert-butyldimethylsilyl glycidyl ether / 1.) THF, -78 -> 23 deg C, 2.) THF, -5 deg C, 11 h 2: 97 percent / diethyl ether / -78 - 0 °C
  • 34
  • [ 124150-87-4 ]
  • (3S,5R)-5-(tert-Butyl-dimethyl-silanyloxymethyl)-3-methyl-dihydro-furan-2-one [ No CAS ]
YieldReaction ConditionsOperation in experiment
Multi-step reaction with 2 steps 1: 1.) lithium N,N-diisopropylamide, lithium chloride, 2.) (R)-(+)-tert-butyldimethylsilyl glycidyl ether / 1.) THF, -78 -> 23 deg C, 2.) THF, -5 deg C, 10 h 2: 90 percent / sulfuric acid / H2O; dioxane / 0.33 h / 95 °C
  • 35
  • [ 124150-87-4 ]
  • [ 1066-54-2 ]
  • [ 1083005-62-2 ]
YieldReaction ConditionsOperation in experiment
98% Stage #1: trimethylsilylacetylene With n-butyllithium In tetrahydrofuran; hexane at -78℃; for 0.666667h; Stage #2: tert-butyldimethylsilyl (R)-glycidyl ether With boron trifluoride diethyl etherate In tetrahydrofuran; hexane at -78 - 20℃; Further stages;
  • 36
  • [ 10160-87-9 ]
  • [ 124150-87-4 ]
  • [ 1111316-27-8 ]
YieldReaction ConditionsOperation in experiment
91% Stage #1: Propiolaldehyde diethyl acetal With n-butyllithium In tetrahydrofuran; hexane at -78℃; Stage #2: tert-butyldimethylsilyl (R)-glycidyl ether In tetrahydrofuran; hexane at -78℃; Stage #3: With boron trifluoride diethyl etherate In tetrahydrofuran; hexane at -78 - -30℃;
  • 37
  • [ 114377-38-7 ]
  • [ 124150-87-4 ]
  • [ 1044739-97-0 ]
YieldReaction ConditionsOperation in experiment
55% In methanol at 20 - 50℃;
  • 38
  • [ 124150-87-4 ]
  • 1-O-tert-butyldimethylsilyl-3-iodo-sn-glycerol [ No CAS ]
YieldReaction ConditionsOperation in experiment
93% With C4H8O*I2Mg In dichloromethane at 20℃; for 0.0166667h; regioselective reaction;
  • 39
  • [ 124150-87-4 ]
  • [ 1178587-36-4 ]
YieldReaction ConditionsOperation in experiment
92% With C4H8O*Br2Mg In dichloromethane at 20℃; for 0.0166667h; regioselective reaction;
  • 40
  • [ 124150-87-4 ]
  • [ 1178587-37-5 ]
YieldReaction ConditionsOperation in experiment
20% With magnesium chloride In dichloromethane at 20℃; for 0.0166667h; regioselective reaction;
  • 41
  • [ 57531-37-0 ]
  • [ 124150-87-4 ]
  • [ 1162654-54-7 ]
  • [ 1162654-60-5 ]
  • 42
  • [ 13683-41-5 ]
  • [ 124150-87-4 ]
  • [ 1162676-14-3 ]
YieldReaction ConditionsOperation in experiment
99% Stage #1: 1-bromo-1-(trimethylsilyl)ethene With magnesium In tetrahydrofuran at 60℃; for 0.75h; Inert atmosphere; Reflux; Stage #2: tert-butyldimethylsilyl (R)-glycidyl ether With copper(l) cyanide In tetrahydrofuran at -30 - 20℃; for 2.08333h; Inert atmosphere;
  • 43
  • [ 75-77-4 ]
  • [ 124150-87-4 ]
  • (R)-1-Azido-3-(tert-butyl-dimethyl-silanyloxy)-2-trimethylsilanyloxy-propane [ No CAS ]
YieldReaction ConditionsOperation in experiment
Stage #1: tert-butyldimethylsilyl (R)-glycidyl ether With sodium azide; ammonium chloride Stage #2: chloro-trimethyl-silane With triethylamine optical yield given as %ee;
  • 44
  • tert-butyldimethylsilyl glycidyl ether [ No CAS ]
  • [ 1214921-58-0 ]
  • (2R)-1-[tert-butyl(dimethyl)silyl]oxy-3-fluoro-propan-2-ol [ No CAS ]
  • [ 124150-87-4 ]
YieldReaction ConditionsOperation in experiment
With (R,R)-(-)-N,N′-bis(3,5-di-tert-butylsalicylidene)-1,2-cyclohexanediaminocobalt(II); 1,1,1,3',3',3'-hexafluoro-propanol; benzoyl fluoride; DBN In diethyl ether at 20℃; for 24h; Resolution of racemate; optical yield given as %ee; enantioselective reaction;
  • 45
  • [ 923686-35-5 ]
  • [ 124150-87-4 ]
  • [ 1216844-68-6 ]
YieldReaction ConditionsOperation in experiment
70% With N-benzyl-N,N,N-triethylammonium chloride; caesium carbonate In 1,4-dioxane; N,N-dimethyl-formamide at 110℃; for 0.333333h; Inert atmosphere; Microwave irradiation;
  • 46
  • [ 2181-42-2 ]
  • [ 124150-87-4 ]
  • (R)-1-(tert-butyldimethylsilyloxy)but-3-en-2-ol [ No CAS ]
YieldReaction ConditionsOperation in experiment
90% Stage #1: trimethylsulphonium iodide With n-butyllithium In tetrahydrofuran at -25℃; for 0.5h; Inert atmosphere; Schlenk technique; Stage #2: tert-butyldimethylsilyl (R)-glycidyl ether In tetrahydrofuran at 0 - 20℃; for 2.5h; Inert atmosphere; Schlenk technique;
72% With n-butyllithium In tetrahydrofuran; hexane at -10 - 20℃;
Stage #1: trimethylsulphonium iodide With n-butyllithium In tetrahydrofuran; hexane at -20℃; Inert atmosphere; Stage #2: tert-butyldimethylsilyl (R)-glycidyl ether In tetrahydrofuran; hexane at -20 - 20℃; Inert atmosphere; Stage #3: With water; ammonium chloride In tetrahydrofuran; hexane; ethyl acetate 8.1 n-Butyllithium (58.2 mL, 2.64 M solution in hexane) was added dropwise to a suspension of trimethylsulfonium iodide (32.4 g) in tetrahydrofuran (400 mL) in a nitrogen atmosphere at -20° C. The reaction solution was stirred at the same temperature for 30 minutes. tert-Butyldimethylsilyl (R)-(-)-glycidyl ether (10 g) was added dropwise to the reaction solution at the same temperature. The reaction solution was stirred for three hours with gradual heating to room temperature. Aqueous ammonium chloride and ethyl acetate were added to the reaction solution, and the organic layer was separated. The organic layer was washed with saturated aqueous sodium chloride twice. The organic layer was dried over anhydrous magnesium sulfate and concentrated under reduced pressure. The residue was purified by silica gel column chromatography to obtain the title compound (9.6 g).1H-NMR (400 MHz, CDCl3) δ (ppm): 0.08 (s, 6H), 0.91 (s, 9H), 2.56 (d, J=3.6 Hz, 1H), 3.45 (dd, J=7.6, 10.0 Hz, 1H), 3.66 (dd, J=4.0, 10.0 Hz, 1H), 4.14-4.20 (m, 1H), 5.19 (ddd, J=1.6, 1.6, 10.8 Hz, 1H), 5.35 (ddd, J=1.6, 1.6, 17.6 Hz, 1H), 5.81 (ddd, J=6.0, 10.4, 17.6 Hz, 1H).
  • 47
  • [ 2039-88-5 ]
  • [ 124150-87-4 ]
  • C11H12O [ No CAS ]
YieldReaction ConditionsOperation in experiment
Stage #1: 2-bromostyrene With n-butyllithium In tetrahydrofuran; hexane at -78℃; for 0.166667h; Inert atmosphere; Stage #2: With copper(l) iodide In tetrahydrofuran; hexane at -78 - -30℃; Inert atmosphere; Stage #3: tert-butyldimethylsilyl (R)-glycidyl ether In tetrahydrofuran; hexane at -30 - 20℃; Inert atmosphere;
  • 48
  • [ 2039-88-5 ]
  • [ 124150-87-4 ]
  • [ 1228752-98-4 ]
YieldReaction ConditionsOperation in experiment
21% Stage #1: 2-bromostyrene With n-butyllithium In tetrahydrofuran; hexane at -78℃; for 0.166667h; Inert atmosphere; Stage #2: With copper(l) iodide In tetrahydrofuran; hexane at -78 - -30℃; Inert atmosphere; Stage #3: tert-butyldimethylsilyl (R)-glycidyl ether Further stages;
  • 49
  • [ 75-16-1 ]
  • [ 124150-87-4 ]
  • [ 133649-29-3 ]
YieldReaction ConditionsOperation in experiment
Stage #1: methylmagnesium bromide With copper(l) iodide In tetrahydrofuran; diethyl ether at -78℃; for 0.583333h; Stage #2: tert-butyldimethylsilyl (R)-glycidyl ether In tetrahydrofuran; diethyl ether at -78℃; for 2h; Synthesis of (R)-5-ethyl-2,2,8,8,9,9-hexamethyl-3,3-diphenyl-4,7-dioxa-3,8-disiladecane (8): A suspension of copper iodide (5.4 g, 28.3 mmol) in tetrahydrofuran (190 mL) was cooled to -78 °C and methyl magnesium bromide (3 M in diethyl ether, 120 mL, 360 mmol) was added via an addition funnel over 20 min. The mixture was stirred at -78 °C for 15 min and then a solution of epoxide 4a in tetrahydrofuran (90 mL) was added via an addition funnel over 20 min. The reaction was stirred at -78 °C for 2 h. After this time, the reaction was diluted with hexanes (100 mL) and then quenched carefully with a saturated aqueous ammonium chloride solution (350 mL). The mixture was further diluted with hexanes/ethyl acetate (10:3, 250 mL). The aqueous layer was separated and extracted with hexanes/ethyl acetate (7:3, 2 ×100 mL). The combined organic layers were washed with brine (100 mL), dried over sodium sulfate, and then filtered through a pad of diatomaceous earth. The filtrate, containing alcohol 4b, was concentrated to a volume of 70 mL and then diluted with anhydrous dichloromethane (250 mL). To this solution was added imidazole (27.7 g, 405 mmol) and 4-dimethylaminopyridine (1.67 g, 13.5 mmol). The mixture was cooled to 0 °C and tert-butylchlorodiphenylsilane (90 mL, 351 mmol) was added. The reaction was stirred at room temperature for 17 h. After this time, the reaction was diluted with hexanes (750 mL) and loaded on a silica gel plug. Purification by passing through a plug of silica gel (10 × 13 cm, 4:1 hexanes/dichloromethane) afforded 8 (115g, 86% for three steps) as a colorless oil:
With copper(l) iodide In tetrahydrofuran at -30℃; for 2.5h;
  • 50
  • [ 124150-87-4 ]
  • [ 1309610-37-4 ]
YieldReaction ConditionsOperation in experiment
Multi-step reaction with 2 steps 1.1: copper(l) iodide / tetrahydrofuran; diethyl ether / 0.58 h / -78 °C 1.2: 2 h / -78 °C 2.1: 1H-imidazole; dmap / dichloromethane / 17 h / 0 - 20 °C
Multi-step reaction with 2 steps 1: copper(l) iodide / tetrahydrofuran / 2.5 h / -30 °C 2: 1H-imidazole; dmap / dichloromethane / 17 h / 10 - 20 °C
  • 51
  • [ 81790-10-5 ]
  • [ 124150-87-4 ]
  • [ 1352746-56-5 ]
YieldReaction ConditionsOperation in experiment
60% Stage #1: (2-bromoallyl)trimethylsilane With iodine; magnesium In tetrahydrofuran Inert atmosphere; Reflux; Stage #2: tert-butyldimethylsilyl (R)-glycidyl ether With copper(l) iodide; magnesium In tetrahydrofuran at -10℃; for 1h; Inert atmosphere; Stage #3: With water; ammonium chloride In tetrahydrofuran for 1h; 4.2.27. (2R)-1-tert-Butyldimethylsilyloxy-4-(trimethylsilylmethyl)-pent-4-en-2-ol (42) The bromopropenylsilane 40 (12.05 g, 62.4 mmol) and two small crystals of iodine were added to a suspension of magnesium (1.67 g, 68.7 mmol) in THF (10 mL). After 10 min, the iodine colouration disappeared and the reaction mixture became warm. After the reflux stopped, the mixture was heated under reflux for 5 min. The resulting green/brown solution was allowed to cool to room temperature and added dropwise via cannula to a mixture of the epoxide 41 (11.73 g, 62.4 mmol) and copper(I) iodide (1.19 g, 6.24 mmol) in THF (40 mL) at -10° C. More THF (10 mL) was added to the residual magnesium and this was also added to the reaction mixture that was stirred at -10° C for 1 h. Saturated aqueous ammonium chloride (30 mL) was added and the mixture exposed to the air. After 1 h, the mixture was extracted with ether (3×30 mL) and the organic extracts were washed with water (30 mL) and brine (30 mL) then dried over magnesium sulfate. After concentration under reduced pressure, chromatography of the residue eluting with light petroleum to light petroleum/ether (1:1) gave the title compound42 (11.1 g, 60%) as a colourless oil, Rf=0.5 (1:1 light petroleum/ethyl acetate), [α]D -0.1 (c 2.6 in Et2O); νmax/cm-1 3468, 2954, 2930, 2859, 1632, 1463, 1417, 1250, 1114, 1039, 840 and 777; δH (300 MHz, CDCl3) 0.00 (9H, s, 3× SiCH3), 0.04 (6H, s, 2× SiCH3), 0.88 [9H, s, SiC(CH3)3], 1.54 and 1.55 (each 1H, d, J 13.3, 4-CH), 2.09 (2H, m, 3-H2), 2.32 (1H, d, J 3.1, OH), 3.47 (1H, dd, J 9.9 and 6.5, 1-H), 3.57 (1H, dd, J 9.9 and 4.3, 1-H'), 3.76 (1H, m, 2-H) and 4.61 and 4.66 (each 1H, s, 5-H); δC (75 MHz, CDCl3) -5.45, -5.42, -1.46, 18.20, 25.81, 26.65, 42.02, 66.62, 69.68, 109.88 and 144.02.
  • 52
  • [ 17049-49-9 ]
  • [ 124150-87-4 ]
  • [ 862848-63-3 ]
YieldReaction ConditionsOperation in experiment
100% Stage #1: octylmagnesium bromide With dimethylsulfide In tetrahydrofuran; diethyl ether at -78℃; for 1h; Inert atmosphere; Stage #2: tert-butyldimethylsilyl (R)-glycidyl ether In tetrahydrofuran; diethyl ether at -78 - 0℃; for 3h; Inert atmosphere; regioselective reaction;
  • 53
  • [ 107-00-6 ]
  • [ 124150-87-4 ]
  • C13H26O2Si [ No CAS ]
YieldReaction ConditionsOperation in experiment
73% Stage #1: but-1-yne With n-butyllithium In tetrahydrofuran at -78℃; for 0.25h; Inert atmosphere; Stage #2: tert-butyldimethylsilyl (R)-glycidyl ether With boron trifluoride diethyl etherate In tetrahydrofuran at -78℃; for 3h; Inert atmosphere;
With n-butyllithium; boron trifluoride diethyl etherate In tetrahydrofuran at -78℃;
  • 54
  • [ 76782-82-6 ]
  • [ 124150-87-4 ]
  • [ 1365694-10-5 ]
YieldReaction ConditionsOperation in experiment
77% With n-butyllithium; boron trifluoride diethyl etherate In tetrahydrofuran at -78℃;
  • 55
  • [ 124150-87-4 ]
  • (R)-1-(t-butyldimethylsilyloxy)-2-(t-butyldiphenylsilyloxy)hept-4-yne [ No CAS ]
YieldReaction ConditionsOperation in experiment
Multi-step reaction with 2 steps 1: n-butyllithium; boron trifluoride diethyl etherate / tetrahydrofuran / -78 °C 2: 1H-imidazole; dmap / dichloromethane / 20 °C
Multi-step reaction with 2 steps 1.1: n-butyllithium / tetrahydrofuran / 0.25 h / -78 °C / Inert atmosphere 1.2: 3 h / -78 °C / Inert atmosphere 2.1: 1H-imidazole; dmap / dichloromethane / 0 - 20 °C / Inert atmosphere
  • 57
  • [ 501-53-1 ]
  • [ 107-11-9 ]
  • [ 124150-87-4 ]
  • [ 1402931-46-7 ]
  • [ 1402931-47-8 ]
YieldReaction ConditionsOperation in experiment
1: 0.31 g 2: 0.92 g Stage #1: 1-amino-2-propene; tert-butyldimethylsilyl (R)-glycidyl ether In methanol at 50℃; for 4h; Inert atmosphere; Stage #2: benzyl chloroformate With sodium hydrogencarbonate In chloroform; water at 0 - 20℃; Inert atmosphere;
  • 59
  • [ 124150-87-4 ]
  • [ 1402931-44-5 ]
YieldReaction ConditionsOperation in experiment
Multi-step reaction with 2 steps 1.1: dilithium tetrachlorocuprate(II) / tetrahydrofuran / 0.67 h / -40 °C / Inert atmosphere 2.1: sodium hydrogencarbonate; ozone / dichloromethane / 1 h / -78 °C 2.2: 12 h / -78 - 20 °C
  • 60
  • [ 124150-87-4 ]
  • [ 1402931-48-9 ]
YieldReaction ConditionsOperation in experiment
Multi-step reaction with 2 steps 1.1: methanol / 4 h / 50 °C / Inert atmosphere 1.2: 0 - 20 °C / Inert atmosphere 2.1: sodium hydrogencarbonate; ozone / dichloromethane / 1 h / -78 °C 2.2: 12 h / -78 - 20 °C
  • 61
  • [ 124150-87-4 ]
  • C39H50O10Si [ No CAS ]
YieldReaction ConditionsOperation in experiment
Multi-step reaction with 3 steps 1.1: dilithium tetrachlorocuprate(II) / tetrahydrofuran / 0.67 h / -40 °C / Inert atmosphere 2.1: sodium hydrogencarbonate; ozone / dichloromethane / 1 h / -78 °C 2.2: 12 h / -78 - 20 °C 3.1: triphenylphosphine / toluene / 0.17 h / 0 °C / Inert atmosphere 3.2: 10 h / 0 °C / Inert atmosphere; Molecular sieve
  • 62
  • [ 124150-87-4 ]
  • C46H55NO12Si [ No CAS ]
YieldReaction ConditionsOperation in experiment
Multi-step reaction with 3 steps 1.1: methanol / 4 h / 50 °C / Inert atmosphere 1.2: 0 - 20 °C / Inert atmosphere 2.1: sodium hydrogencarbonate; ozone / dichloromethane / 1 h / -78 °C 2.2: 12 h / -78 - 20 °C 3.1: triphenylphosphine / toluene / 0.17 h / 0 °C / Inert atmosphere; Molecular sieve 3.2: 6 h / 0 °C / Inert atmosphere
  • 63
  • [ 124150-87-4 ]
  • C38H49NO10Si [ No CAS ]
YieldReaction ConditionsOperation in experiment
Multi-step reaction with 4 steps 1.1: methanol / 4 h / 50 °C / Inert atmosphere 1.2: 0 - 20 °C / Inert atmosphere 2.1: sodium hydrogencarbonate; ozone / dichloromethane / 1 h / -78 °C 2.2: 12 h / -78 - 20 °C 3.1: triphenylphosphine / toluene / 0.17 h / 0 °C / Inert atmosphere; Molecular sieve 3.2: 6 h / 0 °C / Inert atmosphere 4.1: palladium 10% on activated carbon; hydrogen / methanol / 760.05 Torr / Inert atmosphere
  • 64
  • [ 124150-87-4 ]
  • C39H51NO10Si [ No CAS ]
YieldReaction ConditionsOperation in experiment
Multi-step reaction with 5 steps 1.1: methanol / 4 h / 50 °C / Inert atmosphere 1.2: 0 - 20 °C / Inert atmosphere 2.1: sodium hydrogencarbonate; ozone / dichloromethane / 1 h / -78 °C 2.2: 12 h / -78 - 20 °C 3.1: triphenylphosphine / toluene / 0.17 h / 0 °C / Inert atmosphere; Molecular sieve 3.2: 6 h / 0 °C / Inert atmosphere 4.1: palladium 10% on activated carbon; hydrogen / methanol / 760.05 Torr / Inert atmosphere 5.1: sodium tris(acetoxy)borohydride; acetic acid / tetrahydrofuran; methanol; water / 3 h / 20 °C / Inert atmosphere
  • 65
  • [ 124150-87-4 ]
  • C46H55NO12Si [ No CAS ]
YieldReaction ConditionsOperation in experiment
Multi-step reaction with 3 steps 1.1: methanol / 4 h / 50 °C / Inert atmosphere 1.2: 0 - 20 °C / Inert atmosphere 2.1: sodium hydrogencarbonate; ozone / dichloromethane / 1 h / -78 °C 2.2: 12 h / -78 - 20 °C 3.1: triphenylphosphine / toluene / 0.17 h / 0 °C / Inert atmosphere; Molecular sieve 3.2: 6 h / 0 °C / Inert atmosphere
  • 66
  • [ 124150-87-4 ]
  • C38H49NO10Si [ No CAS ]
YieldReaction ConditionsOperation in experiment
Multi-step reaction with 4 steps 1.1: methanol / 4 h / 50 °C / Inert atmosphere 1.2: 0 - 20 °C / Inert atmosphere 2.1: sodium hydrogencarbonate; ozone / dichloromethane / 1 h / -78 °C 2.2: 12 h / -78 - 20 °C 3.1: triphenylphosphine / toluene / 0.17 h / 0 °C / Inert atmosphere; Molecular sieve 3.2: 6 h / 0 °C / Inert atmosphere 4.1: palladium 10% on activated carbon; hydrogen / methanol / 760.05 Torr / Inert atmosphere
  • 67
  • [ 1416908-18-3 ]
  • [ 124150-87-4 ]
  • C35H41ClN2O5 [ No CAS ]
YieldReaction ConditionsOperation in experiment
With potassium carbonate In ethanol at 20 - 120℃; for 0.1h; Sealed vial; Microwave irradiation; 130 Example 130: (S)-1-(4-Chloro-phenyl)-2-(4-{1-[1-((R)-2,3-dihydroxy-propyl)-piperidin-4- -1-hydroxy-ethyl}-phenyl)-7-isopropoxy-6-methoxy-1 ,4-dihydro-2H-isoquinolin-3-oneTo a solution of intermediate 75.1 (75 mg, 0.137 mmol) in ethanol (1 ml) was added potassium carbonate (37.8 mg, 0.273 mmol) followed by (R)-tert-butyldimethyl(oxiran-2- ylmethoxy)silane (38.6 mg, 0.205 mmol) at room temperature. The vial was sealed and kept in the microwave for 6 minutes at 120°C. The reaction mixture was diluted with ethyl acetate and the organic phase was washed with water and brine. The organic phase was dried over Na2S04, filtered and concentrated in vacuo to obtain a yellowish oil.
  • 68
  • [ 1401728-34-4 ]
  • [ 124150-87-4 ]
  • [ 1401729-00-7 ]
YieldReaction ConditionsOperation in experiment
With potassium carbonate In ethanol at 120℃; for 0.1h; Microwave irradiation; 17.A Step A: (R)-1-(tert-butyl-dimethyl-silanyloxy)-3-(4-{(E)-3-[4-(2-ethyl-5,7-dimethyl-pyrazolo[1,5-]pyrimidin-3-ylmethyl)-phenyl]-allyl}-piperazin-1-yl)-propan-2-ol (R'"=TBDMS) 2-Ethyl-5,7-dimethyl-3-[4-((E)-3-piperazin-1-yl-propenyl)-benzyl]-pyrazolo[1,5-a]pyrimidine (example 14) (150 mg, 0.32 mmol) and (R)-tert-butyldimethyl(oxiran-2-ylmethoxy)silane (0.1 ml, 0.32 mmol) and K2CO3 (90 mg, 0.65 mmol) were dissolved in 0.9 ml of ethanol and stirred for 6 min at 120° C. in the microwave. The reaction mixture was concentrated under reduced pressure. The residue was purified via chromatography (silica gel, methanol/EtOAc (0-40%)) to give a yellow oil. MS (ESI): 578 [M+H]+, 1H-NMR (DMSO-d6, 600 MHz) δ (ppm): 7.29 (d, 2H), 7.12 (d, 2H), 6.75 (s, 1H), 6.44 (m, 1H), 6.18 (m, 1H), 4.32 (br, 1H), 4.02 (s, 2H), 3.59 (m, 1H), 3.49 (m, 2H), 3.02 (m, 2H), 2.67 (q, 2H), 2.63 (s, 3H), 2.49-2.5 (m, 8H), 2.48 (s, 3H), 2.35 (m, 1H), 2.20 (m, 1H), 1.13 (t, 3H), 0.85 (s, 9H), 0.03 (s, 6H).
  • 69
  • [ 124150-87-4 ]
  • [ 1066-54-2 ]
  • [ 1220354-16-4 ]
YieldReaction ConditionsOperation in experiment
Multi-step reaction with 2 steps 1.1: n-butyllithium / tetrahydrofuran / 0.25 h / -78 °C / Inert atmosphere 1.2: 3 h / -78 °C / Inert atmosphere 2.1: 1H-imidazole; dmap / dichloromethane / 0 - 20 °C / Inert atmosphere
Multi-step reaction with 2 steps 1.1: n-butyllithium / tetrahydrofuran / 0.25 h / -78 °C 1.2: 3 h / -78 °C 2.1: 1H-imidazole; dmap / dichloromethane / 0 - 20 °C
  • 70
  • [ 65902-59-2 ]
  • [ 124150-87-4 ]
  • (R)-1-(2-bromo-4-nitro-1H-imidazol-1-yl)-3-((tert-butyldimethylsilyl)oxy)propan-2-ol [ No CAS ]
YieldReaction ConditionsOperation in experiment
50% With potassium carbonate In ethanol at 78℃; for 3h;
  • 71
  • [ 527-73-1 ]
  • [ 124150-87-4 ]
  • (R)-1-((tert-butyldimethylsilyl)oxy)-3-(2-nitro-1H-imidazol-1-yl)propan-2-ol [ No CAS ]
YieldReaction ConditionsOperation in experiment
32% With potassium carbonate In ethanol at 78℃; for 2h;
  • 72
  • [ 133398-13-7 ]
  • [ 124150-87-4 ]
  • C28H58O4Si [ No CAS ]
YieldReaction ConditionsOperation in experiment
Stage #1: (R)-10-methyloctadecanoic acid With [(S,S)-N,N’-bis(3,5-di-tertbutylsalicylidene)-1,2-cyclohexanediaminato(2-)]cobalt(II) In diethyl ether at 21℃; for 0.25h; Inert atmosphere; Schlenk technique; Stage #2: With N-ethyl-N,N-diisopropylamine for 0.0833333h; Inert atmosphere; Schlenk technique; Stage #3: tert-butyldimethylsilyl (R)-glycidyl ether for 16h; Inert atmosphere; Schlenk technique;
  • 73
  • [ 57-11-4 ]
  • [ 124150-87-4 ]
  • [ 110193-08-3 ]
YieldReaction ConditionsOperation in experiment
Stage #1: stearic acid With [(S,S)-N,N’-bis(3,5-di-tertbutylsalicylidene)-1,2-cyclohexanediaminato(2-)]cobalt(II) In diethyl ether at 21℃; for 0.25h; Inert atmosphere; Schlenk technique; Stage #2: With N-ethyl-N,N-diisopropylamine for 0.0833333h; Inert atmosphere; Schlenk technique; Stage #3: tert-butyldimethylsilyl (R)-glycidyl ether for 16h; Inert atmosphere; Schlenk technique; regioselective reaction;
  • 74
  • [ 36653-82-4 ]
  • [ 124150-87-4 ]
  • [ 115226-11-4 ]
YieldReaction ConditionsOperation in experiment
With (S,S)-(salen)Co(III)-OTs In tetrahydrofuran at 21℃; for 72h; Schlenk technique;
  • 75
  • [ 124-07-2 ]
  • [ 124150-87-4 ]
  • C17H36O4Si [ No CAS ]
YieldReaction ConditionsOperation in experiment
100% Stage #1: Octanoic acid With [(S,S)-N,N’-bis(3,5-di-tertbutylsalicylidene)-1,2-cyclohexanediaminato(2-)]cobalt(II) In neat (no solvent) at 21℃; Inert atmosphere; Schlenk technique; Stage #2: With N-ethyl-N,N-diisopropylamine Inert atmosphere; Schlenk technique; Stage #3: tert-butyldimethylsilyl (R)-glycidyl ether for 16h; Inert atmosphere; Schlenk technique; regioselective reaction;
  • 76
  • [ 124150-87-4 ]
  • [ 1066-54-2 ]
  • [ 1613271-07-0 ]
YieldReaction ConditionsOperation in experiment
Stage #1: trimethylsilylacetylene With sec.-butyllithium In tert-butyl methyl ether; cyclohexane at 0 - 5℃; for 3h; Inert atmosphere; Stage #2: tert-butyldimethylsilyl (R)-glycidyl ether With copper(l) iodide In tert-butyl methyl ether; cyclohexane at -83 - 20℃; for 18h; Inert atmosphere; 4 Example 4: (/f)-l-((tert-butyldimethylsilyl)oxy)-6-(trimethylsilyl)hex-5-yn-2-ol (3a). Example 4: (/f)-l-((tert-butyldimethylsilyl)oxy)-6-(trimethylsilyl)hex-5-yn-2-ol (3a). [0345] To a 3-neck flask fitted with a mechanical stirrer, a thermocouple and addition funnel was charged l-(trimethylsilyl)-l-propyne (120.0 g, 1.07 mol, 2.2 equiv) followed by ieri-butyl methyl ether (600 mL) while being kept under nitrogen. The solution was cooled to 0 + 5 °C while stirring and sec-butyllithium (696 mL, mmol, 2.0 equiv, 2 M in cyclohexane) was added slowly while maintaining the reaction temperature below 5 °C. After complete addition, the resulting mixture was stirred at 0 + 5 °C under nitrogen for three hours. In a separate 3-neck flask fitted with a mechanical stirrer, a thermocouple, and addition funnel was charged epoxide 2a (92.5 g, 0.49 mol, 1.0 equiv) followed by tert-butyl methyl ether (1800mL) and copper iodide (18.6 g, 0.1 mol, 0.2 equiv) while being kept under nitrogen. The resulting mixture was cooled to -78 °C + 5 °C and then the l-(trimethylsilyl)-l-propyne solution was cannulated into the epoxide reaction mixture. The resulting reaction mixture was allowed to slowly warm to room temperature. After stirring for 18 hours, the reaction was judged complete by TLC. The reaction was quenched with addition of 5% aqueous citric acid (1500 mL), the layers were separated and the lower aqueous layer was extracted with heptane (1000 mL). The combined organic phases were filtered through a pad of celite (150 g) and the filtrate was concentrated under reduced pressure to give 147 g (-100%) of the title compound as a dark yellow/brown oil. This material was used in the next step without purification. Data for 3a: Rf = 0.55 (20% EtOAc / heptane); *H NMR (400 MHz, CDC13) δ 3.72-3.82 (m, 1H), 3.65 (dd, 7=3.81, 9.96 Hz, 1H), 3.45 (dd, 7=7.03, 9.96 Hz, 1H), 2.47 (d, 7=3.81 Hz, 1H), 2.34-2.42 (m, 2H), 1.63 (q, 7=7.13 Hz, 2H), 0.91 (s, 9H), 0.14 (s, 9H), 0.08 (s, 6H); MS (ESI+) m/z 324.4 (M+Na+).
  • 77
  • [ 1777-03-3 ]
  • [ 124150-87-4 ]
  • 1-((tert-butyldimethylsilyl)oxy)-5-(triethylsilyl)pent-4-yn-2-ol [ No CAS ]
YieldReaction ConditionsOperation in experiment
83% Stage #1: 2-triethylsilylacetylene With n-butyllithium In tetrahydrofuran; hexane at -78℃; for 0.5h; Stage #2: With boron trifluoride diethyl etherate In tetrahydrofuran; hexane at -78℃; for 0.333333h; Stage #3: tert-butyldimethylsilyl (R)-glycidyl ether In tetrahydrofuran; hexane at -78℃; for 1h;
  • 78
  • [ 6224-91-5 ]
  • [ 124150-87-4 ]
  • [ 1613271-07-0 ]
YieldReaction ConditionsOperation in experiment
Stage #1: trimethyl(prop-1-ynyl)silane With sec.-butyllithium In tert-butyl methyl ether; cyclohexane at 0 - 5℃; for 3h; Inert atmosphere; Stage #2: tert-butyldimethylsilyl (R)-glycidyl ether With copper(l) iodide In tert-butyl methyl ether; cyclohexane at -78 - 20℃; for 18h; Inert atmosphere; 4 Example 4: (R)-l-((tert-butyldimethylsilyl)oxy)-6-(trimethylsilyl)hex-5-yn-2-ol (3a). [0326] To a 3 -neck flask fitted with a mechanical stirrer, a thermocouple and addition funnel was charged l-(trimethylsilyl)-l-propyne (120.0 g, 1.07 mol, 2.2 equiv) followed by ter/-butyl methyl ether (600 mL) while being kept under nitrogen. The solution was cooled to 0 ± 5 °C while stirring and sec-butyllithium (696 mL, mmol, 2.0 equiv, 2 M in cyclohexane) was added slowly while maintaining the reaction temperature below 5 °C. After complete addition, the resulting mixture was stirred at 0 ± 5 °C under nitrogen for three hours. In a separate 3-neck flask fitted with a mechanical stirrer, a thermocouple, and addition funnel was charged epoxide 2a (92.5 g, 0.49 mol, 1.0 equiv) followed by tert-butyl methyl ether (1800mL) and copper iodide (18.6 g, 0.1 mol, 0.2 equiv) while being kept under nitrogen. The resulting mixture was cooled to -78 °C ± 5 °C and then the l-(trimethylsilyl)-l-propyne solution was cannulated into the epoxide reaction mixture. The resulting reaction mixture was allowed to slowly warm to room temperature. After stirring for 18 hours, the reaction was judged complete by TLC. The reaction was quenched with addition of 5% aqueous citric acid (1500 mL), the layers were separated and the lower aqueous layer was extracted with heptane (1000 mL). The combined organic phases were filtered through a pad of celite (150 g) and the filtrate was concentrated under reduced pressure to give 147 g (-100%) of the title compound as a dark yellow/brown oil. This material was used in the next step without purification. Data for 3a: Rf = 0.55 (20% EtOAc / heptane); NMR (400 MHz, CDC13) δ 3.72-3.82 (m, 1H), 3.65 (dd, J=3.81, 9.96 Hz, 1H), 3.45 (dd, J=7.03, 9.96 Hz, 1H), 2.47 (d, J=3.81 Hz, 1H), 2.34-2.42 (m, 2H), 1.63 (q, J=7.13 Hz, 2H), 0.91 (s, 9H), 0.14 (s, 9H), 0.08 (s, 6H); MS (ESI+) m/z 324.4 (M+Na+).
  • 79
  • [ 124150-87-4 ]
  • [ 197219-01-5 ]
  • (2R)-1-(t-butyldimethylsilyl)oxy-8-((4-methoxyphenyl)methoxy)oct-4-yn-2-ol [ No CAS ]
YieldReaction ConditionsOperation in experiment
63% Stage #1: 1-methoxy-4-pent-4-ynyloxymethyl-benzene With n-butyllithium In tetrahydrofuran at -78℃; for 0.25h; Inert atmosphere; Stage #2: tert-butyldimethylsilyl (R)-glycidyl ether With boron trifluoride diethyl etherate In tetrahydrofuran for 4h; Inert atmosphere;
  • 80
  • [ 35320-23-1 ]
  • [ 124150-87-4 ]
  • (2R)-2-[(2R)-[(tert-butyl(dimethyl)silyl)oxy]-2-hydroxypropyl]amino}propan-1-ol [ No CAS ]
YieldReaction ConditionsOperation in experiment
In isopropyl alcohol at 80℃; A (2R)-2-[((2R)-{tert-butyl(dimethyl)silyl]oxy}-2-hydroxypropyl)amino]propan-1-ol (A-2) (2R)-2-[((2R)-{tert-butyl(dimethyl)silyl]oxy}-2-hydroxypropyl)amino]propan-1-ol (A-2) A solution of A-1 (5.2 g, 27.6 mmol) in 100 mL of 2-propanol was treated with 2-amino-1-propanol (6.22 g, 83 mmol) and heated to 80°C overnight. Solvent was concentrated and the resulting residue was diluted with EtOAc and washed with saturated aqueous NaHCO3 and brine, and dried over Na2SO4. The organic extracts were concentrated to provide A-2 as a white solid. Data for A-2: LRMS m/z (M + H) = 264.04 found; 264.45 required
  • 81
  • [ 124150-87-4 ]
  • [ 176175-97-6 ]
  • C22H30F2O3Si [ No CAS ]
YieldReaction ConditionsOperation in experiment
71% Stage #1: 1-benzyloxy-3,5-difluorobenzene With phenyllithium In tetrahydrofuran; diethyl ether; cyclohexane at -78℃; for 1h; Stage #2: tert-butyldimethylsilyl (R)-glycidyl ether With boron trifluoride diethyl etherate In tetrahydrofuran; diethyl ether; cyclohexane at -78 - 20℃; for 1h; regioselective reaction;
  • 82
  • [ 124150-87-4 ]
  • [ 176175-97-6 ]
  • C31H50F2O3Si2 [ No CAS ]
YieldReaction ConditionsOperation in experiment
Multi-step reaction with 2 steps 1.1: phenyllithium / tetrahydrofuran; cyclohexane; diethyl ether / 1 h / -78 °C 1.2: 1 h / -78 - 20 °C 2.1: 2,6-dimethylpyridine / dichloromethane / 5 h / 0 - 20 °C
  • 83
  • [ 2622-05-1 ]
  • [ 124150-87-4 ]
  • [ 900519-19-9 ]
YieldReaction ConditionsOperation in experiment
98% In tetrahydrofuran; diethyl ether at -30 - 20℃; for 3h; Inert atmosphere;
  • 84
  • [ 74965-31-4 ]
  • [ 124150-87-4 ]
  • C21H37NO4Si [ No CAS ]
YieldReaction ConditionsOperation in experiment
Stage #1: N-(tert-butoxycarbonyl)-o-toluidine With sec.-butyllithium In tetrahydrofuran; cyclohexane at -40℃; for 0.5h; Inert atmosphere; Stage #2: tert-butyldimethylsilyl (R)-glycidyl ether In tetrahydrofuran; cyclohexane at -40℃; for 2h; Inert atmosphere; Representativeexample, synthesis of 13a (R1-4 = H): General procedure: To a solution of tert-butyl o-tolylcarbamate (10a, 3.57 g, 17.2 mmol) in THF (25 mL) under N2 at -40 °C (ACN/dry ice bath) was added sec-butyllithium (1.4 M soln in cyclohexane, 25.1 mL, 35.1 mmol). Stirring was continued for 30 min at which time a solution of (S)-tert-butyldimethyl(oxiran-2-ylmethoxy)silane (8, 2.70 g, 14.3 mmol) in THF (15mL) was added. Stirring was continued at-40 °C for 2 h at which time the mixture was quenched with sat. aq. NH4Cl. The cooling bath was removed, the mixture was warmed to rt and extracted with EtOAc. The organics were washed with brine, dried over MgSO4, filtered, and concentrated. Purification by silica gel chromatography (15% EtOAc in hexanes gradient to 40% EtOAc in hexanes) gave (S)-tert-butyl(2-(4-((tert-butyldimethylsilyl)oxy)-3-hydroxybutyl)phenyl)carbamate (11a, 6.09 g, approx. 80 wt.% purity by 1H NMR) as a clear oil. 1H NMR (400 MHz, CDCl3): δ 7.80(1H, m), 7.56 (1H, br s), 7.19 (1H, td, J = 7.7, 1.8 Hz), 7.13 (1H, dd, J = 7.6, 1.8 Hz), 7.02 (1H, dd, J = 7.5, 1.4 Hz), 3.54 (1H, dd, J = 9.6, 3.2 Hz), 3.52 (1H, m), 3.38 (1H,dd, J = 9.6, 7.3 Hz), 2.85-2.67 (3H, m),1.72 (1H, m), 1.63 (1H, m), 1.52 (9H, s), 0.90 (9H, s), 0.06 (3H, s), 0.03 (3H,s). LCMS (ESI+): m/z396.4 [M + H]+. The material was used directly in next reaction without further purification.
  • 85
  • (R)-ethyl 4-((1R,3aS,5aR,5bR,7aR,11aS,11bR,13aR,13bR)-3a-amino-5a,5b,8,8,11a-pentamethyl-1-(prop-1-en-2-yl)-2,3,3a,4,5,5a,5b,6,7,7a,8,11,11a,11b,12,13,13a,13b-octadecahydro-1H-cyclopenta[a]chrysen-9-yl)-1-(((3-cyanopyridin-2-yl)oxy)methyl)cyclohex-3-ene-1-carboxylate [ No CAS ]
  • [ 124150-87-4 ]
  • [ 76-05-1 ]
  • (R)-ethyl 4-((1R,3aS,5aR,5bR,7aR,11aS,11bR,13aR,13bR)-3a-(((R)-3-((tert-butyldimethylsilyl)oxy)-2-hydroxypropyl)amino)-5a,5b,8,8,11a-pentamethyl-1-(prop-1-en-2-yl)-2,3,3a,4,5,5a,5b,6,7,7a,8,11,11a,11b,12,13,13a,13b-octadecahydro-1H-cyclopenta[a]chrysen-9-yl)-1-(((3-cyanopyridin-2-yl)oxy)methyl)cyclohex-3-ene-1-carboxylate trifluoroacetate [ No CAS ]
YieldReaction ConditionsOperation in experiment
Stage #1: (R)-ethyl 4-((1R,3aS,5aR,5bR,7aR,11aS,11bR,13aR,13bR)-3a-amino-5a,5b,8,8,11a-pentamethyl-1-(prop-1-en-2-yl)-2,3,3a,4,5,5a,5b,6,7,7a,8,11,11a,11b,12,13,13a,13b-octadecahydro-1H-cyclopenta[a]chrysen-9-yl)-1-(((3-cyanopyridin-2-yl)oxy)methyl)cyclohex-3-ene-1-carboxylate; tert-butyldimethylsilyl (R)-glycidyl ether In 1,4-dioxane; acetonitrile at 100℃; for 19h; Inert atmosphere; Stage #2: trifluoroacetic acid In water; acetonitrile A7.4; A8.4 Step 4. Preparation of (R)-ethyl 4-((1R,3aS,5aR,5bR,7aR,11aS,11bR,13aR,13bR)-3a-(((R)-3-((tert-butyldimethylsilyl)oxy)-2-hydroxypropyl)amino)-5a,5b,8,8,11a-pentamethyl-1-(prop-1-en-2-yl)-2,3,3a,4,5,5a,5b,6,7,7a,8,11,11a,11b,12,13,13a,13b-octadecahydro-1H-cyclopenta[a]chrysen-9-yl)-1-(((3-cyanopyridin-2-yl)oxy)methyl)cyclohex-3-ene-1-carboxylate TFA. To a solution of (R)-ethyl 4-(( 1R,3a5,5aR,5bR,7aR, 1 laS, 1 ibR, 1 3aR, 1 3bR)-3a- amino-5a,5b, 8,8,11 a-pentamethyl- 1 -(prop-i -en-2-yl)- 2,3,3a,4,5,5a,5b,6,7,7a,8,i 1,1 ia,i ib,12,13,13a,13b-octadecahydro-1H- cyclopenta[ajchrysen-9-yl)- 1 -(((3 -cyanopyridin-2-yl)oxy)methyl)cyclohex-3 -enecarboxylate (48.5 mg, 0.070 mmol) in acetonitrile (0.5 mL) and 1,4-dioxane (0.5 mL) was added tert-butyldimethylsilyl (R)-(-)-glycidyl ether (0.094 mL, 0.489 mmol) and the mixture was stirred at 100 °C overnight. After 19h, the reaction was allowed to cool to RT and was purified by reverse phase preparative HPLC using preparative HPLC method 8 and dried under vacuo to give (R)-ethyl 4-((1 R,3a5,5aR,5bR,7aR, 1 laS, 1 ibR, 1 3aR, 1 3bR)-3a-(((R)-3 -((tert-butyldimethylsilyl)oxy)2-hydroxypropyl)amino)-5a,5b,8,8, ii a-pentamethyl- 1 -(prop-i -en-2-yl)-2,3,3a,4,5,5a,5b,6,7,7a,8,1 1,1 la,1 lb,12,13,13a,13b-octadecahydro-1H- cyclopenta[ajchrysen-9-yl)- 1 -(((3 -cyanopyridin-2-yl)oxy)methyl)cyclohex-3 - enecarboxylate, TFA (22.8 mg, 0.023 mmol, 32.7 % yield, 53.5% yield based on recovered starting material) and recovered starting material (21.9 mg), both as clear glasssolid. LCMS: mlz 882.4 (M+Hj, retention time 1.849 mm (LCMS Method 16).
  • 86
  • [ 100-42-5 ]
  • [ 124150-87-4 ]
  • C17H28O2Si [ No CAS ]
  • C17H28O2Si [ No CAS ]
YieldReaction ConditionsOperation in experiment
99.6 % ee With 1,1'-bis-(diphenylphosphino)ferrocene; tetrakis(triphenylphosphine) palladium(0); triethylammonium iodide In 1,4-dioxane at 110℃; for 48h; Overall yield = 68 %;
  • 87
  • [ 124150-87-4 ]
  • C20H34O4Si [ No CAS ]
YieldReaction ConditionsOperation in experiment
Multi-step reaction with 2 steps 1.1: n-butyllithium / tetrahydrofuran / 0.5 h / -25 °C / Inert atmosphere; Schlenk technique 1.2: 2.5 h / 0 - 20 °C / Inert atmosphere; Schlenk technique 2.1: Hoveyda-Grubbs catalyst second generation / dichloromethane / Inert atmosphere; Schlenk technique; Reflux
  • 88
  • [ 124150-87-4 ]
  • C26H48O5Si2 [ No CAS ]
YieldReaction ConditionsOperation in experiment
Multi-step reaction with 3 steps 1.1: n-butyllithium / tetrahydrofuran / 0.5 h / -25 °C / Inert atmosphere; Schlenk technique 1.2: 2.5 h / 0 - 20 °C / Inert atmosphere; Schlenk technique 2.1: Hoveyda-Grubbs catalyst second generation / dichloromethane / Inert atmosphere; Schlenk technique; Reflux 3.1: N-ethyl-N,N-diisopropylamine / dichloromethane / 15 h / 20 °C / Inert atmosphere; Schlenk technique
  • 89
  • [ 124150-87-4 ]
  • [ 167484-18-6 ]
  • (R)-1'-benzyloxycarbonyl-1-{3-[(tert-butyldimethylsilyl)oxy ]-2-hydroxypropyl}spiro[indoline-3,4'-piperidine] [ No CAS ]
  • C29H42N2O4Si [ No CAS ]
YieldReaction ConditionsOperation in experiment
With potassium carbonate; In ethanol; at 90℃; for 18.6667h; (Reference Example 35) (R)-1'-benzyloxycarbonyl-1-{3-[(tert-butyldimethylsilyl)oxy ]-2-hydroxypropyl}spiro[indoline-3,4'-piperidine] First, the 1'-benzyloxycarbonyl-1-spiro[indoline-3,4'-piperidine] (90.9 mg) was dissolved in ethanol (1 mL), (R)-tert-butyldimethyl(oxiran-2-ylmethoxy)silane (261.4 mg) and potassium carbonate (126.7 mg) were added thereto, and the mixture was stirred at 90 ºC for 18 hours 40 minutes. Water was added to the reaction solution, followed by four times of extraction with ethyl acetate. The organic layer was washed with saturated brine, then was dried with anhydrous sodium sulfate, and was concentrated under reduced pressure. The obtained residue was purified by silica gel column chromatography (ethyl acetate/n-hexane = 0/100 to 40/60) to obtain 115.4 mg of the title compound (a mixture of isomers at about 3:2). 1H-NMR(270MHz, CDCl3) delta: 0.09 (s, 3H), 0.10 0.12 (3:2) (s, 3H), 0.919 0.924 (2:3) (s, 9H), 1.63-1.93 (m, 4H), 2.48 (br.d, J=4.6Hz, 1H), 2.90 -3.09 (m, 2H), 3.18 3.20 (2:3) (s, 2H) , 3.30-3.47 (m,2H), 3.59-3.75 (m,2H), 3.88-4.01 (m , 1H), 4.07-4.22 (m, 2H), 5.17 (s,2H), 6.49-6.56 (m, 1H), 6.66-6.76 (m , 1H), 6.97-7.04 (m, 1H), 7.10 (td, J=7.6, 7.6, 1.3Hz, 1H), 7.28-7.43 ( m, 5H). MS (ESI) m/z:511 [M+H]+.
  • 90
  • [ 124150-87-4 ]
  • (R)-3-((tert-butyldimethylsilyl)oxy)-2-((8-((1R,2S)-2-hexylcyclopropyl)octanoyl)oxy)propyl palmitate [ No CAS ]
YieldReaction ConditionsOperation in experiment
Multi-step reaction with 2 steps 1.1: [(S,S)-N,N’-bis(3,5-di-tertbutylsalicylidene)-1,2-cyclohexanediaminato(2-)]cobalt(II) / diethyl ether / 0.33 h / Inert atmosphere 1.2: 22 h / Inert atmosphere; Sealed tube 2.1: dmap; dicyclohexyl-carbodiimide / n-heptane / 18 h / 0 °C / Inert atmosphere
  • 91
  • [ 124150-87-4 ]
  • (R)-3-((tert-butyldimethylsilyl)oxy)-2-((8-((1S,2R)-2-hexylcyclopropyl)octanoyl)oxy)propyl palmitate [ No CAS ]
YieldReaction ConditionsOperation in experiment
Multi-step reaction with 2 steps 1.1: [(S,S)-N,N’-bis(3,5-di-tertbutylsalicylidene)-1,2-cyclohexanediaminato(2-)]cobalt(II) / diethyl ether / 0.33 h / Inert atmosphere 1.2: 22 h / Inert atmosphere; Sealed tube 2.1: dmap; dicyclohexyl-carbodiimide / n-heptane / 18 h / 0 °C / Inert atmosphere
  • 92
  • [ 124150-87-4 ]
  • C42H82O5Si [ No CAS ]
YieldReaction ConditionsOperation in experiment
Multi-step reaction with 2 steps 1.1: [(S,S)-N,N’-bis(3,5-di-tertbutylsalicylidene)-1,2-cyclohexanediaminato(2-)]cobalt(II) / diethyl ether / 0.33 h / Inert atmosphere 1.2: Inert atmosphere; Sealed tube 2.1: dmap; dicyclohexyl-carbodiimide / n-heptane / 18 h / 0 °C / Inert atmosphere
  • 93
  • [ 124150-87-4 ]
  • (R)-3-((tert-butyldimethylsilyl)oxy)propane-1,2-diyl dipalmitate [ No CAS ]
YieldReaction ConditionsOperation in experiment
Multi-step reaction with 2 steps 1.1: [(S,S)-N,N’-bis(3,5-di-tertbutylsalicylidene)-1,2-cyclohexanediaminato(2-)]cobalt(II) / diethyl ether / 0.33 h / Inert atmosphere 1.2: 22 h / Inert atmosphere; Sealed tube 2.1: dmap; dicyclohexyl-carbodiimide / n-heptane / 18 h / 0 °C / Inert atmosphere
  • 94
  • [ 151766-46-0 ]
  • [ 124150-87-4 ]
  • (R)-3-((tert-butyldimethylsilyl)oxy)-2-hydroxypropyl 8-((1R,2S)-2-hexylcyclopropyl)octanoate [ No CAS ]
  • (R)-3-((tert-butyldimethylsilyl)oxy)-2-((8-((1R,2S)-2-hexylcyclopropyl)octyl)oxy)propyl 8-((1R,2S)-2-hexylcyclopropyl)octanoate [ No CAS ]
YieldReaction ConditionsOperation in experiment
1: 65% 2: 14% Stage #1: 8-((1R,2S)-2-hexylcyclopropyl)octanoic acid With [(S,S)-N,N’-bis(3,5-di-tertbutylsalicylidene)-1,2-cyclohexanediaminato(2-)]cobalt(II) In diethyl ether for 0.333333h; Inert atmosphere; Stage #2: tert-butyldimethylsilyl (R)-glycidyl ether With N-ethyl-N,N-diisopropylamine Inert atmosphere; Sealed tube;
  • 95
  • [ 57-10-3 ]
  • [ 124150-87-4 ]
  • (R)-3-((tert-butyldimethylsilyl)oxy)-2-hydroxypropyl palmitate [ No CAS ]
YieldReaction ConditionsOperation in experiment
77% Stage #1: 1-hexadecylcarboxylic acid With [(S,S)-N,N’-bis(3,5-di-tertbutylsalicylidene)-1,2-cyclohexanediaminato(2-)]cobalt(II) In diethyl ether for 0.333333h; Inert atmosphere; Stage #2: tert-butyldimethylsilyl (R)-glycidyl ether With N-ethyl-N,N-diisopropylamine for 22h; Inert atmosphere; Sealed tube;
  • 96
  • [ 124150-87-4 ]
  • [ 139592-37-3 ]
  • [ 139573-72-1 ]
  • 97
  • tert-butyldimethylsilyl glycidyl ether [ No CAS ]
  • [ 124150-87-4 ]
YieldReaction ConditionsOperation in experiment
50% With [(S,S)-N,N’-bis(3,5-di-tertbutylsalicylidene)-1,2-cyclohexanediaminato(2-)]cobalt(II); acetic acid In tetrahydrofuran; water at 0 - 20℃; for 21h;
  • 98
  • [ 693-04-9 ]
  • [ 124150-87-4 ]
  • [ 1017601-77-2 ]
YieldReaction ConditionsOperation in experiment
Stage #1: butyl magnesium bromide With copper(l) iodide In tetrahydrofuran at -50 - -10℃; for 0.75h; Inert atmosphere; Stage #2: tert-butyldimethylsilyl (R)-glycidyl ether In tetrahydrofuran at -50 - 20℃; Inert atmosphere; Synthesis of compound 7: (S)-1-((tert-butyldimethylsilyl)oxy)heptan-2-ol A a stirring solution of n-butylmagnesium chloride (5, 45.0 mmol, 22.5 mL 2.0 M in THF, 3.0 equiv.) in dry THF (22.5 mL) was added CuI (1.5 mmol, 286 mg, 0.10 equiv.) at -50 °C under argon to give a dark blue mixture. The mixture was stirred for 15 min. at -50 °C, then at -10 °C for 10 minutes, before it was cooled to -50 °C again. After stirring for 20 minutes at -50 °C, a solution of (S)-(+)-tert-butyldimethyl(oxiran-2-ylmethoxy)silane (5, 15.0 mmol, 2.37 g, 1.0 equiv.) in dry THF (10.0 mL) was added dropwise. After stirring for 20 minutes at -50 °C, the cooling bath was removed and the mixture was stirred at room temperature over night. The mixture was quenched by careful addition of sat. aq. NaHCO3 at 0 °C, diluted with diethyl ether and then filtered through a pad of Celite. The aqueous layer was extracted with Et2O (3 x 50 mL) and the organic layers were combined, dried (MgSO4) and evaporated. The residue was purified by flash chromatography on silica gel (10% EtOAc in heptane) to afford the desired product 7 as a colorless oil in 78% yield (2.52 g). 1H NMR (400 MHz, CDCl3) δ 3.68 - 3.55 (m, 2H), 3.38 (dd, J = 10.6 and 8.3 Hz, 1H), 2.40 (bs, 1H), 1.53 - 1.21 (m, 8H), 1.00 - 0.77 (m, 12H), 0.06 (s, 6H). 13C NMR (101 MHz, CDCl3) δ 72.0, 67.4, 32.9, 32.1, 26.0, 25.4, 22.7, 18.4, 14.2, -5.2, -5.3. [α]25D = +6,5 (c=1.0, CHCl3), lit. [α]23D = +7,3 (c=1.0, CHCl3). Rf = 0.25 (EtOAc/heptane 1:9, KMnO4-stain). The spectroscopic data were in agreement with those reported in the literature
  • 100
  • [ 36653-82-4 ]
  • [ 124150-87-4 ]
  • [ 1001440-56-7 ]
YieldReaction ConditionsOperation in experiment
86% With boron trifluoride diethyl etherate In dichloromethane at 0 - 20℃; for 19h; Inert atmosphere;
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