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Structure of 2975-46-4 * Storage: {[proInfo.prStorage]}
* All experimental methods are cited from the reference, please refer to the original source for details. We do not guarantee the accuracy of the content in the reference.
With Iron(III) nitrate nonahydrate; oxygen; sodium 2,2,2-trifluoroacetate In ethyl acetate at 25℃; for 16 h;
General procedure: In a test tube, trans-2-decenal (167 mg, 1.0 mmol) was added to a suspension of Fe(NO3)3·9H2O(4.1 mg, 0.010 mmol) and CF3COONa (28 mg, 0.20 mmol) in EtOAc (0.50 mL). O2 balloon (1atm) was attached at top of the test tube, and inner atmosphere was replaced by O2. After stirring16 h at 25 °C, EtOAc (3 mL) and 1M HCl aq. (1 mL) were added and resulting biphasic mixture wasstirred for 1 min. Organic phase was separated, and water phase was extracted by EtOAc (3 mL X2). To the collected organic phase was then added measured amount of biphenyl (as an internalstandard for NMR analysis). The conversion of substrate and the yield of products weredetermined by NMR analysis (400 MHz, CDCl3, 25 °C). Products were identified by comparison tothe NMR signals of authentic samples. The same reaction was performed twice for each reaction.
Stage #1: With ethylmagnesium bromide In tetrahydrofuran at 10 - 20℃; Inert atmosphere Stage #2: at -25 - 30℃; Stage #3: With sulfuric acid; water In tetrahydrofuran; diethyl ether at 0℃;
d) Preparation of trimethylsilyl-propynalTrimethylsilylethyne (5.0 ml, 36.10 mmol) in THF (25.0 ml) was dropwsise added to a solution of EtMgBr in THF (IM, 44.0 ml, 44.0 mmol) at 10-150C under nitrogen. Once the addition finished, the mixture was stirred at room temperature for one hour and was added over a 30 min. period to an efficiently stirred mixture of DMF (10.0 ml, 123.0 mmol) in Et2O (20.0 ml) at -25°C. The white suspension was allowed to reach room temperature, stirred for one hour, heated at 300C for 15 minutes, and poured into H2SO4 5percent at 00C. The aqueous layer was extracted three times with Et2O, the combined organic layers were washed with a saturated aqueous solution of NH4Cl, dried over Na2SO4, and the solvents were carefully removed under vacuum to give a crude which was further purified by bulb to bulb distillation (20 mBar, room temperature) to afford the title compound (2.255 g) in 49percent yield. 1H NMR: 9.15 (s, IH), 0.25 (s, 9H). 13C NMR: 176.7, 103.0, 102.3, 0.88.
Reference：
[1] Tetrahedron Letters, 1995, vol. 36, # 3, p. 401 - 404
[2] Angewandte Chemie - International Edition, 2008, vol. 47, # 6, p. 1130 - 1133
[3] Tetrahedron, 2002, vol. 58, # 12, p. 2415 - 2422
[4] Arkivoc, 2012, vol. 2012, # 7, p. 253 - 273
[5] Patent: WO2009/141781, 2009, A1, . Location in patent: Page/Page column 18
[6] Journal of Organic Chemistry, 1995, vol. 60, # 14, p. 4331 - 4338
[7] J. Gen. Chem. USSR (Engl. Transl.), 1966, vol. 36, p. 920 - 922[8] Zhurnal Obshchei Khimii, 1966, vol. 36, p. 907 - 909
[9] Tetrahedron, 1983, vol. 39, # 19, p. 3073 - 3082
[10] Chemical and Pharmaceutical Bulletin, 1999, vol. 47, # 3, p. 398 - 404
[11] Synthesis, 2002, # 12, p. 1759 - 1774
[12] Journal of the American Chemical Society, 2013, vol. 135, # 36, p. 13502 - 13511
[13] Chemistry - A European Journal, 2014, vol. 20, # 50, p. 16694 - 16706
[14] Organometallics, 2018, vol. 37, # 9, p. 1346 - 1357
3
[ 183718-76-5 ]
[ 1066-54-2 ]
[ 2975-46-4 ]
Yield
Reaction Conditions
Operation in experiment
90%
Stage #1: With n-butyllithium In hexane Stage #2: at 0℃; for 8 h;
General procedure: To the ice-cold solution of aldehyde in THF was added, the solution of alkylmagnesium halide or alkyllithium in THF (1.3 eq., at 0 °C). The reaction was stirred at 0 °C for 1 h, diluted with saturated aq. NH4Cl (10 mL) and ethyl acetate (10 mL). Aqueous layer was extracted with ethyl acetate (2×10 mL). The combined organic layers were washed with brine (10 mL), and dried over Na2SO4. Evaporation of the solvent and purification of the crude mixture by column chromatography (9:1, hexane: EtOAc) gave the corresponding bisindolylmethane derivatives (BIM) up to 92percent yields along with the by-product aldehyde.
Reference：
[1] Mendeleev Communications, 2005, vol. 15, # 6, p. 263 - 265
[2] Chemistry - A European Journal, 2015, vol. 21, # 27, p. 9662 - 9665
[3] Advanced Synthesis and Catalysis, 2017, vol. 359, # 18, p. 3207 - 3216
[4] Synthesis, 1991, # 11, p. 979 - 982
[5] Bulletin des Societes Chimiques Belges, 1990, vol. 99, # 10, p. 837 - 847
[6] Chemistry - A European Journal, 2005, vol. 11, # 5, p. 1610 - 1624
[7] Synthesis, 2008, # 23, p. 3797 - 3800
[8] Journal of Organic Chemistry, 2009, vol. 74, # 23, p. 9206 - 9209
[9] Journal of the American Chemical Society, 1994, vol. 116, # 14, p. 6121 - 6129
[10] Organic Letters, 2008, vol. 10, # 24, p. 5529 - 5531
[11] European Journal of Organic Chemistry, 2013, # 29, p. 6584 - 6600
[12] Tetrahedron, 1995, vol. 51, # 27, p. 7389 - 7402
[13] European Journal of Organic Chemistry, 2005, # 7, p. 1444 - 1458
[14] Chemistry - A European Journal, 2004, vol. 10, # 20, p. 5087 - 5110
[15] Organic letters, 2002, vol. 4, # 4, p. 565 - 568
[16] Chemistry - A European Journal, 2007, vol. 13, # 19, p. 5378 - 5387
[17] Chemistry of Heterocyclic Compounds, 2006, vol. 42, # 11, p. 1457 - 1463
[18] Chemistry - A European Journal, 2011, vol. 17, # 15, p. 4118 - 4130
[19] Chemistry - A European Journal, 2013, vol. 19, # 39, p. 13017 - 13029
[20] Journal of the American Chemical Society, 2016, vol. 138, # 3, p. 770 - 773
[21] ChemMedChem, 2018, vol. 13, # 11, p. 1124 - 1130
5
[ 104831-79-0 ]
[ 1066-54-2 ]
[ 2975-46-4 ]
Yield
Reaction Conditions
Operation in experiment
82%
Stage #1: With n-butyllithium In hexane Stage #2: at 0℃; for 8 h;
General procedure: To the ice-cold solution of aldehyde in THF was added, the solution of alkylmagnesium halide or alkyllithium in THF (1.3 eq., at 0 °C). The reaction was stirred at 0 °C for 1 h, diluted with saturated aq. NH4Cl (10 mL) and ethyl acetate (10 mL). Aqueous layer was extracted with ethyl acetate (2×10 mL). The combined organic layers were washed with brine (10 mL), and dried over Na2SO4. Evaporation of the solvent and purification of the crude mixture by column chromatography (9:1, hexane: EtOAc) gave the corresponding bisindolylmethane derivatives (BIM) up to 92percent yields along with the by-product aldehyde.
Stage #1: With n-butyllithium In hexane Stage #2: at 0℃; for 8 h;
General procedure: To the ice-cold solution of aldehyde in THF was added, the solution of alkylmagnesium halide or alkyllithium in THF (1.3 eq., at 0 °C). The reaction was stirred at 0 °C for 1 h, diluted with saturated aq. NH4Cl (10 mL) and ethyl acetate (10 mL). Aqueous layer was extracted with ethyl acetate (2×10 mL). The combined organic layers were washed with brine (10 mL), and dried over Na2SO4. Evaporation of the solvent and purification of the crude mixture by column chromatography (9:1, hexane: EtOAc) gave the corresponding bisindolylmethane derivatives (BIM) up to 92percent yields along with the by-product aldehyde.
General procedure: To the ice-cold solution of aldehyde in THF was added, the solution of alkylmagnesium halide or alkyllithium in THF (1.3 eq., at 0 °C). The reaction was stirred at 0 °C for 1 h, diluted with saturated aq. NH4Cl (10 mL) and ethyl acetate (10 mL). Aqueous layer was extracted with ethyl acetate (2×10 mL). The combined organic layers were washed with brine (10 mL), and dried over Na2SO4. Evaporation of the solvent and purification of the crude mixture by column chromatography (9:1, hexane: EtOAc) gave the corresponding bisindolylmethane derivatives (BIM) up to 92percent yields along with the by-product aldehyde.
Stage #1: With n-butyllithium In hexane Stage #2: at 0℃; for 8 h;
General procedure: To the ice-cold solution of aldehyde in THF was added, the solution of alkylmagnesium halide or alkyllithium in THF (1.3 eq., at 0 °C). The reaction was stirred at 0 °C for 1 h, diluted with saturated aq. NH4Cl (10 mL) and ethyl acetate (10 mL). Aqueous layer was extracted with ethyl acetate (2×10 mL). The combined organic layers were washed with brine (10 mL), and dried over Na2SO4. Evaporation of the solvent and purification of the crude mixture by column chromatography (9:1, hexane: EtOAc) gave the corresponding bisindolylmethane derivatives (BIM) up to 92percent yields along with the by-product aldehyde.
With hydrogenchloride; n-butyllithium In diethyl ether; hexane; N,N-dimethyl-formamide
Example 2 Ethynyltrimethylsilane (5.0 g, 50.9 mmol) was dissolved in dry diethyl ether (50 ml), 1.6 M n-butyllithium in hexane(35.0 ml, 56.0 mmol) was added dropwise at 0°C under argon atmosphere. The mixture was stirred at the same temperature for 1h. DMF(3.72g, 50.9mmol) was dissolved in diethyl ether (20ml), and was added dropwise below 5°C for 30 min, then the mixture was stirred at room temperature for 2 h. The reaction was quenched by the addition of 2N hydrochloric acid, and the mixture was extracted with diethyl ether. The organic layer was washed with water, saturated sodium hydrogencarbonate solution, and brine in order, and dried over sodium sulfate. Purification by distillation (40-45°C/15mmHg) gave 3-(trimethylsilyl)propiol aldehyde (28percent). Colorless oil 1H-NMR (CDCl3) δ:0.27 (9H, s), 9.17 (1H, s).
Reference：
[1] Patent: EP1145718, 2001, A1,
[2] Chemical Communications, 2006, # 4, p. 383 - 385
10
[ 42201-71-8 ]
[ 2975-46-4 ]
Reference：
[1] Chemical Communications, 2006, # 4, p. 383 - 385
11
[ 50965-66-7 ]
[ 2975-46-4 ]
Reference：
[1] Chemistry - A European Journal, 2004, vol. 10, # 20, p. 5087 - 5110
[2] Bulletin des Societes Chimiques Belges, 1990, vol. 99, # 10, p. 837 - 847
12
[ 5582-62-7 ]
[ 2975-46-4 ]
Reference：
[1] Synthesis, 1991, # 11, p. 979 - 982
13
[ 36551-06-1 ]
[ 2975-46-4 ]
Reference：
[1] Chemistry - A European Journal, 2015, vol. 21, # 27, p. 9662 - 9665
d) Preparation of trimethylsilyl-propynalTrimethylsilylethyne (5.0 ml, 36.10 mmol) in THF (25.0 ml) was dropwsise added to a solution of EtMgBr in THF (IM, 44.0 ml, 44.0 mmol) at 10-150C under nitrogen. Once the addition finished, the mixture was stirred at room temperature for one hour and was added over a 30 min. period to an efficiently stirred mixture of DMF (10.0 ml, 123.0 mmol) in Et2O (20.0 ml) at -25C. The white suspension was allowed to reach room temperature, stirred for one hour, heated at 300C for 15 minutes, and poured into H2SO4 5% at 00C. The aqueous layer was extracted three times with Et2O, the combined organic layers were washed with a saturated aqueous solution of NH4Cl, dried over Na2SO4, and the solvents were carefully removed under vacuum to give a crude which was further purified by bulb to bulb distillation (20 mBar, room temperature) to afford the title compound (2.255 g) in 49% yield. 1H NMR: 9.15 (s, IH), 0.25 (s, 9H). 13C NMR: 176.7, 103.0, 102.3, 0.88.
N-(pyridin-2-yl)-2-trimethylsilylethynyl-1,2-dihydropyridine-3,5-dicarbaldehyde[ No CAS ]
Yield
Reaction Conditions
Operation in experiment
With hydrogenchloride; water; In acetonitrile; at 25℃; for 168h;Sealed tube;
2-Aminopyridine 2 (0.199 g, 2.11 mmol) in acetonitrile (2 ml), 0.05 ml HCl (0.2 M) and 3-trimethylsilyl-2-propyn-1-al 1 (0.267 g, 2.11 mmol) were placed into the glass ampoule and sealed. The ampoule was stored at room temperature and periodically shaken for 7 days. After then it was opened and reaction mixture was diluted to 10 ml with diethyl ether and passed through the column with silica (SiO2, ? 1 cm, height 1 cm). Purified reaction mixture was concentrated in vacuum (1 mmHg) and analyzed by 1H NMR.
Stage #1: 1-((triisopropylsilyl)ethynyl)-4-ethynylbenzene With n-butyllithium In diethyl ether; hexane at -78℃; for 1h;
Stage #2: 3-(trimethylsilyl)prop-2-yn-1-al In diethyl ether; hexane at -78 - 20℃; Further stages.;
3-(1-hydroxy-1-methylethyl)-4-trimethylsilylethynyl-2-azetidinone[ No CAS ]
Yield
Reaction Conditions
Operation in experiment
With diisopropylamine
13 Synthesis of compound (7) STR33
EXAMPLE 13 Synthesis of compound (7) STR33 The reaction procedure of Example 1 is followed using trimethylsilylpropynal (1.26 g), 1,1,1,3,3,3-hexamethyldisilazane (0.61 g) and commercial butyllithium (1.60M)-hexane (6.2 ml) as well as ethyl 3-hydroxy-3-methylbutanoate (1.46 g), diisopropylamine (2.40 g) and commercial butyllithium-hexane (14 ml). The reaction mixture containing the desired product is concentrated under reduced pressure and the residue is subjected to silica gel column chromatography (eluent: 30% ethyl acetate-70% hexane) to give 0.278 g of 3-(1-hydroxy-1-methylethyl)-4-trimethylsilylethynyl-2-azetidinone (1:2 cis-trans mixture). M.p.: 137°-140° C. IR (Nujol): 3500, 3260, 2960, 1735, 1710 cm-1. NMR (CDCl3, ppm) of the cis compound 0.10 (9H, s), 1.33 (6H, s), 2.86 (1H, s) 3.33 (1H, dd, J=6.3 and 2.0 Hz), 4.30 (1H, d, J=6.3 Hz), 6.47 (1H, m). NMR (CDCl3, ppm) of the trans compound 0.10 (9H, s), 1.13 (3H, s), 1.40 (3H, s), 2.06 (1H, s), 3.16 (1H, d, J=3.3 Hz), 4.13 (1H, d, J=3.3 Hz), 6.30 (1H, m).
(1S,4R)-2-methyl-3-methylene-bicyclo[2.2.1]heptane[ No CAS ]
[ 1193457-47-4 ]
Yield
Reaction Conditions
Operation in experiment
b) Preparation of (lR,4S)-l-(3-Methyl-bicyclo[2.2.1]hept-2-en-2-yl)-but-3-yn-2-ol: via ene-reactionMe2AlCl (IM in hexanes, 23.7 ml, 23.7 mmol) was added dropwise to a solution of trimethylsilyl-propynal (3.74 g; 80% pure, 23.7 mmol) and (lS,2S,4R)-2-endo-methyl-3- methylene-bicyclo[2.2.1]heptane (4.25; 65% pure; containing 25% of exo-isomer;22.6 mmol) in dichloromethane (80 ml) containing a few crystals of BHT at -78C under <n="28"/>nitrogen. The mixture was stirred at -78C for 15 minutes and was poured into aqueous HCl 5%. The product was extracted with ether. The combined organic layers were washed with water, cone. NaHCtheta3 solution, brine, dried over Na2SO4 and filtered off to give a crude which was bulb-to-bulb distilled (0.07 mbar/ oven temp. 1200C) to afford ( 1 R,4S)- 1 -(3-methyl-bicyclo [2.2.1 ]hept-2-en-2-yl)-4-trimethylsilanyl-but-3 -yn-2-ol(4.84 g; 66% pure).
(+/-)-2-endo-methyl-3-methylene-bicyclo[2.2.1]heptane[ No CAS ]
1-(3-methyl-bicyclo[2.2.1]hept-2-en-2-yl)-4-trimethylsilanyl-but-3-yn-2-ol[ No CAS ]
Yield
Reaction Conditions
Operation in experiment
59%
e) Preparation of l-(3-Methyl-bicyclo[2.2.1]hept-2-en-2-yl)-4-trimethylsilanyl-but-3- yn-2-ol via ene-reactionMe2AlCl (IM in hexanes, 1.1 ml, 1.1 mmol) was dropwise added to a solution of trimethylsilyl-propynal (154.0 mg, 1.22 mmol) and 2-endo-methyl-3-methylene- bicyclo[2.2.1]heptane (140.0 mg, 1.15 mmol) in dichloromethane (5.0 ml) at -78C under nitrogen. The mixture was stirred at -78C for 15 minutes and was hydrolyzed with aqueous HCl 5%. The temperature was then slowly allowed to increase to room temperature and extracted twice with CH2Cl2. The combined organic layers were washed with water, brine, dried over Na2SO4 and filtered off to give a crude which was further purified by flash chromatography with cyclohexane/ AcOEt (97/3) as eluent to afford title compound (148.0 mg) in 59% yield. <n="20"/>Ene -reaction could also be performed at -78C with BF3 Et2O (5 mol%) as catalyst in dichloromethane at -78C with complete conversion in 5 minutes.
A suspension of (3-phthalidyl)triphenylphosphonium bromide (Howe 1973) (2) (503 mg, 1.06 mmol), which had been prepared from 1, 3- <strong>[2975-46-4]trimethylsilylpropynal</strong> (100 mg, 1.06 mmol), and Et3N (148 muL, 1.06 mmol) in tetrahydrofuran (8 mL) is stirred for 1 h, then at reflux (80 C) for 2 h, and a room temperature for 16 h, and then filtered. A mixture of the residue obtained from concentration of the filtrate, hydrazine monohydrate (55 muL, 1.14 mmol), and ethanol (8 mL) is heated at reflux (90 0C) for 5 h. Solvent is removed at reduced pressure, and the residue is diluted with water (20 mL) and extracted (ethyl acetate). The residue obtained on work-up is chromatographed (20% to 50% ethyl acetate/hexane) to give 172 mg (63%) of 3 as a cream solid, mp 198-200 C. IR 2903, 1694, 1122 cm"1; 1H NMR delta 0.15 (s, 9H, TMS), 3.91 (s, 2H, CH2), 7.79-7.93 (m, 2H, 6,7-PhthH), 8.08 (dd, J= 8.1 Hz, 1.2 Hz, IH, 5-PhthH), 8.50 (dd, J = 7.8 Hz, 1.8 Hz, IH, 8-PhthH), 10.25 ppm (bs, IH, NH). HRMS calcd Ci4H16N2OSi [M + H]+ 257.1105, found 257.1109.
4-[(2R,3S,4R,5S)-3-(3-chloro-2-fluoro-phenyl)-4-(4-chloro-2-fluoro-phenyl)-4-cyano-5-(2,2-dimethyl-propyl)-1-(3-trimethylsilanyl-prop-2-ynyl)-pyrrolidine-2-carbonyl]-amino}-3-methoxy-benzoic acid[ No CAS ]
Yield
Reaction Conditions
Operation in experiment
88.5%
In a round-bottomed flask, chiral 4-[(2R,3S,4R,5S)-3-(3-chloro-2-fluoro-phenyl)-4-(4-chloro-2-fluoro-phenyl)-4-cyano-5-(2,2-dimethyl-propyl)-pyrrolidine-2-carbonyl]-amino}-3-methoxy-benzoic acid methyl ester (50.0 mg, 79.3 mumol) and 3-<strong>[2975-46-4]trimethylsilylpropynal</strong> (0.1 mL, 0.792 mmol) were combined with AcOH (0.60 mL) and stirred at rt. Sodium triacetoxyborohydride (Fluka, 150 mg, 0.708 mmol) was added in two portions, 30 min apart and vigorously stirred for 3 h. The reaction mixture was diluted with 0.1 N NaOH and extracted with EtOAc. The organic layer was separated and concentrated under reduced pressure to afford crude product chiral 4-[(2R,3S,4R,5S)-3-(3-chloro-2-fluoro-phenyl)-4-(4-chloro-2-fluoro-phenyl)-4-cyano-5-(2,2-dimethyl-propyl)-1-(3-trimethylsilanyl-prop-2-ynyl)-pyrrolidine-2-carbonyl]-amino}-3-methoxy-benzoic acid (52 mg, 88.5%) that was carried directly to the next step.
diethyl 4-(trimethylsilylethynyl)-2,6-dimethyl-1,4-dihydropyridine-3,5-dicarboxylate[ No CAS ]
Yield
Reaction Conditions
Operation in experiment
82%
With acetic acid; In toluene; at 100℃; for 0.0166667h;Microwave irradiation; Sealed tube;
3-Component Hantzsch DHP synthesis in a single-mode microwave batch reactor (Table 3, entry 5). A mixture of 3-(trimethylsilyl)propynal (14d, 50 mg, 0.53 mmol) and ethyl beta-aminocrotonate (11, 0.14 g, 1.1 mmol) in PhMe-glacial acetic acid (5:1, 2 mL) was irradiated at 100 C for 1 min in a sealed tube using a CEM Discover microwave synthesizer at an initial power of 70 W. The reaction mixture was cooled in a stream of compressed air and partitioned between saturated aqueous NaHCO3 solution (25 mL) and EtOAc (25 mL). The aqueous layer was further extracted with EtOAc (2 × 15 mL) and the combined organic extracts were washed with brine (15 mL), dried (Na2SO4) and evaporated in vacuo to give the title compound (0.15 g, 82%) as a yellow solid, mp 137-138 C (aq EtOH); (Found: [M + H]+, 350.1783. C18H27NO4Si, [M + H] requires 350.1782); Rf 0.47 (light petroleum-EtOAc, 1:1); IR (nujol)/cm-1: 3302, 3244, 3107, 1699, 1661, 1636, 1503, 1328,1301, 1208, 1120, 1095, 1026, 840; 1H NMR (400 MHz,CDCl3) delta 5.69 (br s, 1H, NH), 4.72 (s, 1H, 4-H), 4.11 (m, 2H, OCHHCH3), 4.08 (m, 2H, OCHHCH3), 2.20 (s, 6H, 2,6-CH3),1.21 (t, J 7.1, 6H, OCH2CH3), 0.00 (s, 9H, SiMe3); 13C NMR (100 MHz, CDCl3) delta 167.0 (C), 144.9 (C), 109.8 (C), 100.2 (C),82.5 (C), 59.8 (CH2), 27.6 (CH), 19.5 (CH3), 14.4 (CH3), 0.22(CH3); MS (APcI) m/z (rel intensity): 350 (MH+, 100%), 252(15), 178 (15), 113 (10).
diethyl 4-(trimethylsilylethynyl)-2,6-dimethyl-1,4-dihydropyridine-3,5-dicarboxylate[ No CAS ]
Yield
Reaction Conditions
Operation in experiment
84%
With ammonium acetate; acetic acid; In ethanol; at 120℃; for 0.116667h;Microwave irradiation; Sealed tube;
4-Component Hantzsch DHP synthesis in a single-mode microwave batch reactor (Table 3, entry 6). A solution of 3-(trimethylsilyl)propynal (14d) (50 mg, 0.53 mmol), ethylacetoacetate (11) (0.14 g, 1.1 mmol) and ammonium acetate (0.12 g, 1.6 mmol) in EtOH-glacial acetic acid (5:1, 2 mL) was irradiated at 120 C for 7 min in a sealed tube using a CEM Discover microwave synthesizer at an initial power of 90 W. The reaction mixture was cooled in a stream of compressed air and evaporated in vacuo. The residue was partitioned between saturated aqueous NaHCO3 solution (25 mL) and CH2Cl2 (25 mL). The aqueous layer was further extracted with CH2Cl2 (2 × 15 mL) and the organic extracts were combined, washed with brine (15 mL), dried (Na2SO4) and evaporated in vacuo to give the title compound (0.16 g, 84%) as a pale yellow solid, with identical physical and spectroscopic properties.
(Z)-1-(trimethylsilyl)propyl-5-(tert-butyldimethylsilyloxy)-4-trimethylsilylmethyl-pent-4-en-2-ol[ No CAS ]
Yield
Reaction Conditions
Operation in experiment
55%
With diethylaluminium chloride; In dichloromethane; at -78 - 0℃; for 3h;Inert atmosphere;
General procedure: In a 100 mL RBF flushed with argon, aldehyde(19.0 mmol, 5.0 equiv) and TBS allylsilane 12 (1.0 g, 3.76 mmol,1.0 equiv) were dissolved in dry CH2Cl2 (30 mL). Et2AlCl (1 M inCH2Cl2, 1.5 equiv) was syringed into the solution at 78 C. Thereaction mixture was allowed to warm up to 0 C and stirred for3 h. The solution was quenched with satd NaHCO3 (10 mL) andextracted with CH2Cl2 (3 15 mL). The combined organic phaseswere dried over MgSO4, filtered and concentrated under reducedpressure. The crude yellow oil was purified by column chromatographywith pet. ether/EtOAc (7:3) as eluent to afford pure eneproduct
55%
With diethylaluminium chloride; In dichloromethane; at -78 - 0℃; for 3h;
In a 100 mL RBF flushed with argon, aldehyde(19.0 mmol, 5.0 equiv) and TBS allylsilane 12 (1.0 g, 3.76 mmol,1.0 equiv) were dissolved in dry CH2Cl2 (30 mL). Et2AlCl (1 M inCH2Cl2, 1.5 equiv) was syringed into the solution at 78 C. Thereaction mixture was allowed to warm up to 0 C and stirred for3 h. The solution was quenched with satd NaHCO3 (10 mL) andextracted with CH2Cl2 (3 15 mL). The combined organic phaseswere dried over MgSO4, filtered and concentrated under reducedpressure. The crude yellow oil was purified by column chromatographywith pet. ether/EtOAc (7:3) as eluent to afford pure eneproduct.
55%
With diethylaluminium chloride; In dichloromethane; at -78 - 0℃; for 3h;
In a 100 mL RBF flushed with argon, aldehyde(19.0 mmol, 5.0 equiv) and TBS allylsilane 12 (1.0 g, 3.76 mmol,1.0 equiv) were dissolved in dry CH2Cl2 (30 mL). Et2AlCl (1 M inCH2Cl2, 1.5 equiv) was syringed into the solution at 78 C. Thereaction mixture was allowed to warm up to 0 C and stirred for3 h. The solution was quenched with satd NaHCO3 (10 mL) andextracted with CH2Cl2 (3 15 mL). The combined organic phaseswere dried over MgSO4, filtered and concentrated under reducedpressure. The crude yellow oil was purified by column chromatographywith pet. ether/EtOAc (7:3) as eluent to afford pure eneproduct.
Ref. 9 Dimethylpyrrole(1 g, 10 mmol) was put in a round bottom flask under nitrogenatmosphere, and 22 mL of dried dichloromethane were added. Theresulting mixture was sparged with nitrogen bubbling for 90 min.Then 3-(trimethylsilyl)-2-propynal (0.733 mL, 5 mmol) was addeddrop wise at 70 C over a period of 30 min. The solution becamepurple. After the addition, stirring was carried on for 15 more minutesand removed. The solution was allowed to come to room temperatureduring 3 h. The solution became orange. First, p-Chloranil(1.23 g, 10 mmol) was added, the reaction mixture was stirred for1 h until it turned purple. Then, triethylamine (6.74 mL, 50 mmol)was added, the reaction was stirred for 30 min at room temperature.Finally, boron trifluoride diethyl etherate was added drop wise andthe reaction was stirred for 16 h. Dichloromethane was added to themixture and the organic phase was extracted with dichloromethane,washed with water and dried over magnesium sulphate.The solvent was removed under reduced pressure. Acetone wasadded until there was no more smoke emission, and was removedunder reduced pressure. The solid obtained was subjected to columnchromatography (silica gel, using a petroleum ether: dichloromethanemixture (70:30 vol) as the eluent). Yield = 70%.1H NMR (300 MHz, CDCl3, 300 K): d (ppm) = 0,27 (s, 9H); 2.5 (s,6H); 2.4 (s, 6H); 6.04 (s, 2H). 13C NMR {1H} (75 MHz, CDCl3, 300 K):d (ppm) = 0.56; 14.73; 15.65; 100.62; 115.11; 120.20; 120.91;133.21; 142.37; 154.55. ESI-MS: m/z = 345 [M+H]+; 325 [MF]+;367 [M+Na]+ (calcd for C18H23BF2N2Si: 344.17 (exact mass);344.28 (FW)).
α-phenyl-N-[3-(trimethylsilyl)-2-propyn-1-ylidene]benzenemethanamine[ No CAS ]
Yield
Reaction Conditions
Operation in experiment
94%
In dichloromethane; at 0 - 20℃;Inert atmosphere; Molecular sieve;
4.3.1 Synthesis of N-benzhydryl-3-(trimethylsilyl)prop-2-yn-1-imine (14a) 3-Trimethylsilylpropynal 14 (0.564 g, 4.47 mmol) in CH2Cl2 (8.0 mL) was added to a solution of diphenylmethylamine (0.744 g, 4.06 mmol) in CH2Cl2 (5.0 mL) in the presence of molecular sieves 4 A (3.0 g) at 0 C. The reaction mixture was warmed to room temperature and stirred for 20 min. The reaction mixture was filtered through a Celite pad to remove the molecular sieves. The solvents were evaporated in vacuo and then the residue was dried under reduced pressure to give imine 14a as a dark orange oil (1.11 g, 94% yield, E/Z=60:40). The imine 14a was used without further purification: E/Z=60:40; 1H NMR (400 MHz, CDCl3) delta 7.67 (d, J=1.4 Hz, 0.40H), 7.65 (s, 0.60H), 7.21-7.37 (m, 10H), 6.21 (s, 0.40H) 5.47 (s, 0.60H), 0.26 (s, 3.60H), 0.22 (s, 5.40H); 13C NMR (101 MHz, CDCl3) delta 145.3, 143.3, 142.6, 142.4, 128.5, 128.4, 127.7, 127.2, 127.0, 105.1, 101.3, 99.3, 96.7, 78.7, 72.4, -0.6; IR (neat) 3084, 3062, 3027, 2960, 2898, 2853, 1608, 1493, 1453, 1252, 1073, 1033, 847, 760, 746, 700 cm-1; HRMS (EI) calcd for C19H21NSi (M)+ 291.1443, found 291.1457.
(3S)-1-(Trimethylsilyl)tetradeca-1,4-diyn-3-ol[ No CAS ]
Yield
Reaction Conditions
Operation in experiment
55%
General procedure: 3.1.2. General procedure for enantioselective addition of terminalalkynes to aldehydes. A 25 mL flask was charged with Zn(OTf)2(4 equiv) and () or () N-methylephedrine (4 equiv) and purgedwith dry argon for 15 min. Then, DCM (10 mL) and triethylamine(4 equiv) were added. The resulting mixture was vigorously stirredfor 2 h at rt before addition in one portion of a solution of the alkyne(4 equiv) in DCM (15 mL). After 1 h stirring, 3-trimethylsilylpropiolaldehyde (1 equiv) was added, and the mixturewas stirred at rt overnight. After treatment with a saturatedaqueous NH4Cl solution, the aqueous layer was extracted with DCM(310 mL). The collected organic layers were combined, washedwith brine and concentrated under reduced pressure. The crudeproduct was submitted to chromatography over silica gel(Rf0.3e0.4, PE/Et2O 9:1) to give the targeted enantio-enricheddialkynylcarbinol in high yield.; 3.1.9. (3S)-1-(Trimethylsilyl)tetradeca-1,4-diyn-3-ol (S)-8. Using()-N-methylephedrine, obtained as a colorless oil (99 mg, 55%). Rf(PE/Et2O 9:1)0.4., 1H NMR (300 MHz, CDCl3): d0.19 (s, 9H), 0.88(t, J6.9 Hz, 3H), 1.27e1.44 (m, 12H), 1.52 (m, 2H), 2.22 (td, J2.1,6.6 Hz, 2H), 2.37 (d, J6.6 Hz, 1H), 5.10 (br s, 1H); 13C {1H} NMR(75 MHz, CDCl3): d0.0 (3C), 14.4, 19.0, 23.0, 28.6, 29.2, 29.4, 29.6,29.8, 32.2, 53.0, 77.6, 86.1, 89.0, 103.0 ppm; IR (neat): n3366, 2956,2925, 2855, 2291, 2232, 2178, 1465, 1408, 1377, 1329, 1296, 1249,1141, 1030, 961, 840, 759, 721, 700, 669, 617, 599, 580, 573, 560,555 cm1; MS (DCI, NH3): m/z (%): 296.2 (90) [MNH4], 278.1(100) [MH]; HRMS (DCI-CH4): m/z [MH] calcd for C17H29OSi:277.1988, found: 277.1997. optical rotation [a]D20 0.54 (c 0.0515,CHCl3). A 93% ee was estimated for (S)-8 from the chiral SFC analysisof the corresponding 1-naphthyl carbamate 10.
(3R)-1-(trimethylsilyl)tetradeca-1,4-diyn-3-ol[ No CAS ]
Yield
Reaction Conditions
Operation in experiment
50%
General procedure: 3.1.2. General procedure for enantioselective addition of terminalalkynes to aldehydes. A 25 mL flask was charged with Zn(OTf)2(4 equiv) and () or () N-methylephedrine (4 equiv) and purgedwith dry argon for 15 min. Then, DCM (10 mL) and triethylamine(4 equiv) were added. The resulting mixture was vigorously stirredfor 2 h at rt before addition in one portion of a solution of the alkyne(4 equiv) in DCM (15 mL). After 1 h stirring, 3-trimethylsilylpropiolaldehyde (1 equiv) was added, and the mixturewas stirred at rt overnight. After treatment with a saturatedaqueous NH4Cl solution, the aqueous layer was extracted with DCM(310 mL). The collected organic layers were combined, washedwith brine and concentrated under reduced pressure. The crudeproduct was submitted to chromatography over silica gel(Rf0.3e0.4, PE/Et2O 9:1) to give the targeted enantio-enricheddialkynylcarbinol in high yield.; 3.1.10. (3R)-1-(Trimethylsilyl)tetradeca-1,4-diyn-3-ol (R)-8. Using()-N-methylephedrine, obtained as a colorless oil (90 mg, 50%). Rf(PE/Et2O 9:1)0.4. 1H and 13C {1H} NMR, IR and MS data are thesame as those described for (S)-8. [a]D200.51 (c 0.0235, CHCl3). A91% ee was estimated for (R)-8 from the chiral SFC analysis of thecorresponding 1-naphthyl carbamate 10.
(3S)-1-(trimethylsilyl)tricosa-1,4-diyn-3-ol[ No CAS ]
Yield
Reaction Conditions
Operation in experiment
60%
General procedure: 3.1.2. General procedure for enantioselective addition of terminalalkynes to aldehydes. A 25 mL flask was charged with Zn(OTf)2(4 equiv) and () or () N-methylephedrine (4 equiv) and purgedwith dry argon for 15 min. Then, DCM (10 mL) and triethylamine(4 equiv) were added. The resulting mixture was vigorously stirredfor 2 h at rt before addition in one portion of a solution of the alkyne(4 equiv) in DCM (15 mL). After 1 h stirring, 3-trimethylsilylpropiolaldehyde (1 equiv) was added, and the mixturewas stirred at rt overnight. After treatment with a saturatedaqueous NH4Cl solution, the aqueous layer was extracted with DCM(310 mL). The collected organic layers were combined, washedwith brine and concentrated under reduced pressure. The crudeproduct was submitted to chromatography over silica gel(Rf0.3e0.4, PE/Et2O 9:1) to give the targeted enantio-enricheddialkynylcarbinol in high yield.; 3.1.11. (3S)-1-(Trimethylsilyl)tricosa-1,4-diyn-3-ol (S)-9. Using()-N-methylephedrine (87 mg (60%). Rf (PE/Et2O 9:1)0.3. 1HNMR (300 MHz, CDCl3): d0.20 (s, 9H), 0.89 (t, J6.9 Hz, 3H),1.26e1.44 (m, 30H),1.52 (m, 2H), 2.22 (td, J2.0, 7.2 Hz, 2H), 2.58 (d,J7.2 Hz, 1H), 5.11 (dt, J2.0, 7.2 Hz, 1H); 13C {1H} NMR (75 MHz,CDCl3): d0.3 (3C),14.1, 18.8, 22.7, 28.3, 28.9, 29.2, 29.4, 29.5, 29.6,29.7 (8C), 31.9, 52.8, 77.3, 85.9, 88.8, 102.6 ppm; IR (neat): n3324,2957, 2913, 2849, 2313, 2231, 2176, 1471, 1377, 1286, 1250, 1139,1109, 1034, 987, 960, 841, 801, 760, 716, 698, 675, 614, 604, 572,553 cm1; MS (DCI-NH3): m/z (%): 422.3 (100) [MNH4], 404.3(40); HRMS (DCI-CH4): m/z [MH] calcd for C26H49OSi: 405.3553,found: 405.3563. [a]D20 0.23 (c 0.0175 in CHCl3). A 90% ee wasestimated for (S)-9 from the chiral SFC analysis of the corresponding1-naphthyl carbamate 11.
(3R)-1-(trimethylsilyl)tricosa-1,4-diyn-3-ol[ No CAS ]
Yield
Reaction Conditions
Operation in experiment
55%
General procedure: 3.1.2. General procedure for enantioselective addition of terminalalkynes to aldehydes. A 25 mL flask was charged with Zn(OTf)2(4 equiv) and () or () N-methylephedrine (4 equiv) and purgedwith dry argon for 15 min. Then, DCM (10 mL) and triethylamine(4 equiv) were added. The resulting mixture was vigorously stirredfor 2 h at rt before addition in one portion of a solution of the alkyne(4 equiv) in DCM (15 mL). After 1 h stirring, 3-trimethylsilylpropiolaldehyde (1 equiv) was added, and the mixturewas stirred at rt overnight. After treatment with a saturatedaqueous NH4Cl solution, the aqueous layer was extracted with DCM(310 mL). The collected organic layers were combined, washedwith brine and concentrated under reduced pressure. The crudeproduct was submitted to chromatography over silica gel(Rf0.3e0.4, PE/Et2O 9:1) to give the targeted enantio-enricheddialkynylcarbinol in high yield.; 3.1.12. (3R)-1-(Trimethylsilyl)tricosa-1,4-diyn-3-ol (R)-9. Using()-N-methylephedrine, obtained as a white solid (80 mg, 55%). Mp36.9e37.8 C. Yield. Rf (PE/Et2O 9:1)0.3. 1H and 13C {1H} NMR, IRand MS data are the same as those described for (S)-9. [a]D200.26(c 0.046 in CHCl3). A 92% ee was estimated for (rac)-2 from thechiral SFC analysis of the corresponding 1-naphthyl carbamate 11.
(rac)-1-(trimethylsilyl)heptadeca-1,4-diyn-3-ol[ No CAS ]
Yield
Reaction Conditions
Operation in experiment
74%
3.1.5 1-(Trimethylsilyl)heptadeca-1,4-diyn-3-ol (rac)-2 (0022) A 1.6M solution of n-BuLi in hexanes (0.95mL, 1.52mmol) was added dropwise to a stirred solution of 1-tetradecyne (300mg, 1.528mmol) in THF (10mL) at -78C. The reaction mixture was stirred for 1h at this temperature and then for 30min at rt, before cooling again at -78C. Trimethylsilylpropiolaldehyde (211mg, 1.68mmol) was then added and the resulting mixture was stirred overnight. After treatment with saturated aqueous NH4Cl solution and extractions with DCM (3×15mL), the combined organic layers were washed with brine, dried over MgSO4 and evaporated to dryness. The crude residue was purified by silica gel chromatography (Rf=0.3, PE/Et2O 9:1) to give (rac)-2 as a colorless oil (367mg, 74%). 1H NMR (300MHz, CDCl3): delta=0.15 (s, 9H, Si(CH3)3), 0.85 (t, J=6.9Hz, 3H), 1.22-1.39 (m, 18H), 1.49 (pseudo-quint., J=7.1Hz, 2H), 2.18 (td, J=2.1, 7.3Hz 2H), 2.57 (br s, 1H), 5.07ppm (br s, 1H); 13C {1H} NMR (75MHz, CDCl3): delta=-0.4, 14.0, 18.6, 22.6, 28.2, 28.8, 29.0, 29.3, 29.4, 29.5, 29.6 (2C), 31.8, 52.5, 77.3, 85.5, 88.5, 102.7ppm; IR (neat): nu=3368, 2958, 2933, 2860, 2290, 2232, 2177, 1454, 1410, 1379, 1297, 1250, 1142, 1035, 964, 844, 761, 668, 617, 452cm-1; MS (DCI, NH3): m/z (%): 338 (100) [M+NH4]+, 320 (21); HRMS (DCI-CH4): m/z [M+H]+ calcd for C20H36OSi: 320.2535, found: 320.2520.
With Iron(III) nitrate nonahydrate; oxygen; sodium 2,2,2-trifluoroacetate; In ethyl acetate; at 25℃; under 760.051 Torr; for 16h;
General procedure: In a test tube, trans-2-decenal (167 mg, 1.0 mmol) was added to a suspension of Fe(NO3)3·9H2O(4.1 mg, 0.010 mmol) and CF3COONa (28 mg, 0.20 mmol) in EtOAc (0.50 mL). O2 balloon (1atm) was attached at top of the test tube, and inner atmosphere was replaced by O2. After stirring16 h at 25 C, EtOAc (3 mL) and 1M HCl aq. (1 mL) were added and resulting biphasic mixture wasstirred for 1 min. Organic phase was separated, and water phase was extracted by EtOAc (3 mL X2). To the collected organic phase was then added measured amount of biphenyl (as an internalstandard for NMR analysis). The conversion of substrate and the yield of products weredetermined by NMR analysis (400 MHz, CDCl3, 25 C). Products were identified by comparison tothe NMR signals of authentic samples. The same reaction was performed twice for each reaction.
2-[(4-trimethylsilyl-1H-1,2,3-triazol-5-yl)methylidene]malononitrile[ No CAS ]
Yield
Reaction Conditions
Operation in experiment
81%
General procedure: beta-CD (1 mmol) was dissolvedin water (8 ml) by warming to 60 C until a clear solution was formed. Tothis clear solution, acetylenic aldehyde 1a,b (1 mmol) and trimethylsilylazide (1.2 mmol) were added. After stirring for 10 min the solutionof malononitrile (1 mmol) in H2O (2 ml) was added and the mixture wasstirred at room temperature for 4 h until completion of the reaction asindicated by 1H NMR. 1H NMR reaction control was made for selectedportions (1 ml) every hour. The extract from reaction mixture with ethylacetate was evaporated in vacuo and analyzed in DMSO-d6. Then beta-CDwas filtered off, the aqueous phase was extracted with ethyl acetate(3x5 ml). The combined extracts were washed with 5 ml of water anddried over MgSO4. The filtrate was evaporated in vacuo, and columnchromatography of the residue afforded the target compounds.Visualization on TLC was made with iodine vapor.
3,3'-(3-(trimethylsilyl)prop-2-yn-1,1-diyl)bis(1-hexyl-1H-indole)[ No CAS ]
Yield
Reaction Conditions
Operation in experiment
90%
General procedure: To the ice-cold solution of aldehyde in THF was added, the solution of alkylmagnesium halide or alkyllithium in THF (1.3 eq., at 0 C). The reaction was stirred at 0 C for 1 h, diluted with saturated aq. NH4Cl (10 mL) and ethyl acetate (10 mL). Aqueous layer was extracted with ethyl acetate (2×10 mL). The combined organic layers were washed with brine (10 mL), and dried over Na2SO4. Evaporation of the solvent and purification of the crude mixture by column chromatography (9:1, hexane: EtOAc) gave the corresponding bisindolylmethane derivatives (BIM) up to 92% yields along with the by-product aldehyde.
3,3'-(3-(trimethylsilyl)prop-2-yn-1,1-diyl)bis(1-benzyl-5-methoxy-1H-indole)[ No CAS ]
Yield
Reaction Conditions
Operation in experiment
82%
General procedure: To the ice-cold solution of aldehyde in THF was added, the solution of alkylmagnesium halide or alkyllithium in THF (1.3 eq., at 0 C). The reaction was stirred at 0 C for 1 h, diluted with saturated aq. NH4Cl (10 mL) and ethyl acetate (10 mL). Aqueous layer was extracted with ethyl acetate (2×10 mL). The combined organic layers were washed with brine (10 mL), and dried over Na2SO4. Evaporation of the solvent and purification of the crude mixture by column chromatography (9:1, hexane: EtOAc) gave the corresponding bisindolylmethane derivatives (BIM) up to 92% yields along with the by-product aldehyde.
3,3'-(3-(trimethylsilyl)prop-2-yn-1,1-diyl)bis(5-bromo-1-methyl-1H-indole)[ No CAS ]
Yield
Reaction Conditions
Operation in experiment
84%
General procedure: To the ice-cold solution of aldehyde in THF was added, the solution of alkylmagnesium halide or alkyllithium in THF (1.3 eq., at 0 C). The reaction was stirred at 0 C for 1 h, diluted with saturated aq. NH4Cl (10 mL) and ethyl acetate (10 mL). Aqueous layer was extracted with ethyl acetate (2×10 mL). The combined organic layers were washed with brine (10 mL), and dried over Na2SO4. Evaporation of the solvent and purification of the crude mixture by column chromatography (9:1, hexane: EtOAc) gave the corresponding bisindolylmethane derivatives (BIM) up to 92% yields along with the by-product aldehyde.
methyl N-(3-(trimethylsilyl)prop-2-yn-1-yl)-L-tryptophanate[ No CAS ]
Yield
Reaction Conditions
Operation in experiment
84%
Tryptophan methyl ester hydrochloride (0.39mmol,100mg)was measured into a 5mL vial.The amino acid ester was dissolved in 1mL of methanol. Triethylamine(0.78mmol,1.1mL) and 3-(trimethylsilyl)-2-propynal(0.39 mmol,0.058mL) were added via pipette. The solution was stirred in a water/ice bath at 0C for two hours. Sodium borohydride(0.78 mmol,0.030g)was added via four addition sover two hours while maintaining the temperature of the solution below 5C. The solution was transferred, and 2mL diethylether was added.The organic product was extracted with 6M hydrochloric acid(3X1mL). The combined aqueous layers were neutralized with solid potassium bicarbonate. The organic product was extracted with ethylacetate(5X1mL).Organic layers were combined,dried with magnesiumsulfate,filtered and concentrated under nitrogen. Column chromatography gave methyl(3-(trimethylsilyl)prop-2-yn-1-yl)-L-tryptophanate(122mg;84%yield)as a yellow oil;[a]27D=0.3(c1.6,CH3OH);1H-NMR(400MHz,CDCl3)delta8.14(s,1H),7.62(d,J=7.7Hz,1H),7.34(d,J=7.7Hz,1H),7.18(t,J=7.7Hz,1H),7.11(t,J=7.7Hz,1H),7.06(s,1H),3.86(dd,J=5.6,7.5Hz,1H),3.67(s,3H),3.48(d,J=16.9Hz,1H),3.38(d,J=16.9Hz,1H),3.24(dd,J=5.6,14.6Hz,1H),3.13(dd,J=7.5,14.6Hz,1H),0.11(s,9H);13C-NMR(100MHz,CDCl3)delta174.68,136.34,127.48,122.98,122.25,119.63,118.86,111.27,111.08,103.51,88.48,60.27,51.99,37.93, 29.26,--0.01(3C);IR(ATR,Diamond)3408,2954,2360,2168,1732,1457,1434,1340,1249,1206,1122,987,644cm-1;HRMS(CI,methanegas)m/zcalculatedforC18H25N2O2Si[M+H]+329.1680,found329.1669.
methyl N-(3-(trimethylsilyl)prop-2-yn-1-yl)-L-alaninate[ No CAS ]
Yield
Reaction Conditions
Operation in experiment
74%
Alanine methyl ester hydrochloride(0.72mmol,100mg)was measured into a 5mL vial.The amino acid ester was dissolved in 1mL of methanol. Triethylamine(0.72mmol,0.100mL) and 3-(trimethylsilyl)-2-propynal(0.72mmol,0.106mL) were added via pipette. The solution was stirred in a water/ice bath at 0C for two hours. Sodium borohydride(1.44mmol,0.054g)was added via four addition sover two hours while maintaining the temperature of the solution below 5C. The solution was transferred, and 2mL diethylether was added.The organic product was extracted with 6M hydrochloric acid(3X1mL). The combined aqueous layers were neutralized with solid potassium bicarbonate. The organic product was extracted with ethylacetate(5X1mL).Organic layers were combined,dried with magnesiumsulfate,filtered and concentrated under nitrogen.Column chromatography gave methyl(3--(trimethylsilyl)prop-2-yn-1-yl)-L-alaninate (149mg;74%yield)as a yellow oil;[a]26D=-15.6(c2.3,CH3OH);1H-NMR(400MHz,CDCl3)delta3.72(s,3H),3.51(q,J=7.3Hz,1H),3.46(d,J=17.0Hz,1H),3.36(d,J=17.0Hz,1H),1.31(d,J=7.3Hz,3H),0.14(s,9H);13C-NMR(100MHz,CDCl3)delta175.49,103.35,88.41,55.18,52.04,37.62,18.82,0.01(3C);IR(ATR,Diamond)2956,2167,1737,1600,1435,1330,1249,1201,1149,1071,983,839,645,592cm-1;HRMS(CI,methanegas)m/zcalculatedforC10H20NO2Si[M+H]+214.1258,found214.1254.
5-[(4-trimethylsilyl-1H-1,2,3-triazol-5-yl)methylidene]pyrimidine-2,4,6(1H,3H,5H)-trione[ No CAS ]
Yield
Reaction Conditions
Operation in experiment
68%
Trimethylsilyl azide(1 mmol) was added dropwise to a mixture of propynal(1.0 mmol) and water (2 mL), and the mixture was stirred for18 h at room temperature. Barbituric acid (or Meldrums acid)(1.0 mmol) was added, and the mixture was stirred for 20 h atroom temperature. Water (2 mL) was added, and the precipitate was collected on a filter, washed with water and cold methanol, and dried at a reduced pressure.5[(4Trimethylsilyl11,2,3triazol5yl)methylidene]pyrimidine2,4,6(1,3,5)trione (7). Yield 0.19 g (68%).Colorless powder, m.p. >260 (decomp.). 1H NMR (DMSOd6),delta: 0.41 (s, 9 , Me3Si); 8.25 (s, 1 , =); 11.48 (br.s, 2 ,NH(C=O)NH). 13 NMR (DMSOd6), delta: -0.5 (Me3Si); 119.9((7)); 140.5 (C(4)); 143.0 (C(5)); 150.8 (C(10)=O); 163.3(C=); 166.5 (C(12)=); 170.2 (C(8)=). IR (KBr), nu/cm-1:3187, 3066 (NH); 1716 (=); 1709 (=); 1688 (=);1588 (=); 1260, 848, 763 (Me3Si); 1642, 1557, 1474, 1321,1248 (triazole ring). Found (%): , 43.21; H, 4.52; N, 25.14;Si, 10.13. C10H13N5O3Si. Calculated (%): , 43.00; H, 4.69;N, 25.07; Si, 10.05.
1,3-dimethyl-5[(4-trimethylsilyl-1H-1,2,3-triazol-5-yl)methylidene]pyrimidine-2,4,6-(1H,3H,5H)-trione[ No CAS ]
Yield
Reaction Conditions
Operation in experiment
71%
General procedure: Trimethylsilyl azide(1 mmol) was added dropwise to a mixture of propynal(1.0 mmol) and water (2 mL), and the mixture was stirred for18 h at room temperature. Barbituric acid (or Meldrums acid)(1.0 mmol) was added, and the mixture was stirred for 20 h atroom temperature. Water (2 mL) was added, and the precipitate was collected on a filter, washed with water and cold methanol, and dried at a reduced pressure.
General procedure: Step 1. the preparation method of compound 11 isthe same as that of compound 3, except the followingcharacteristics: the 2,2-dimethyl dipropargylmalonate used inembodiment 2 is replaced by 5-cyano-1-pentyne (purchasedfrom 1 & K Technology Co., Ltd., and a trademark numberis 009109) with an equal molar amount.The compound 11 is light yellow oily liquid. Theyield of compound 11 is 81%. The yield of compound 11 iscalculated as a molar amount of the compound 11 divided bya molar amount of 5-cyano-1-pentynex100%. NMR data and high resolution mass spectrometrydata of the compound 11 are as follows.1H NMR delta=5.07 (t, 1=1.85 Hz, 1H), 2.54 (br, 1H),2.48 (t, 1=7.08 Hz, 2H), 2.41 (td, 1=6.74 Hz, 1=1.85 Hz, 2H),1.87 (tt, 1=7.08 Hz, 1=6.74 Hz, 2H), 0.17 (s, 9H); 13C NMR delta=119.23, 102.22, 89.39, 82.51, 79.59, 52.60, 24.29, 17.99,16.23, -0.22. HRMS-ESI (m/z) calculated valueC12H17NOSiNa [M+Na]+ 242.0972, measured value 242.
1,6-heptadiyne (5.0 mL, 4.02 g, 43.63 mmol, purchasedfrom Aladdin Reagent (Shanghai) Co., Ltd., and a trademark number is H102744-25 mL) was dissolved into100 mL tetrahydrofuran under an atmosphere of N2 and magnetic stirring.The solution was cooled to 0C., a solution ofethylmagnesium bromide (1.0 M tetrahydrofuran solution,43.6 mL, and containing ethylmagnesium bromide 43.60mmol) was added gradually within 1 h.The solution reacted for another 1 h at roomtemperature and then cooled to 0C.Trimethylsilylpropynal (7.30 mL, 43.60 mmol)was added rapidly and reacted for 1 h.After reaction, the solution was quenched withsaturated ammonium chloride, and the solution wasextracted with diethyl ether.The organic phase was merged and the organicphase was dried with anhydrous magnesium sulfate.The organic solution was filtrated, concentrated todryness. The residue was chromatographed with silica gel(eluent:n-hexane:ethyl acetate=6:1(v/v)) to obtain 5.71 gcompound 1 as colorless oily liquid. A yield is 60%. (The yield of compound 1 is calculated as a molar amount of thecompound 1 divided by a molar amount of 1 ,6-heptanedynex100%.) NMR data and high resolution mass spectrometrydata of the compound 1 are as follows.1H NMR delta=5.04 (t, 1=1.80 Hz, 1H), 2.69 (br, 1H),2.31 (td, 1=6.99 Hz, 1=1.80 Hz, 2H), 2.25 (td, 1=6.99 Hz,1=2.60 Hz, 2H), 1.93 (t, 1=2.60 Hz, 1H), 1.69 (m, 2H), 0.14(s, 9H); 13C NMRdelta =102.71, 88.81, 84.24, 83.45, 78.31,69.12, 52.59, 27.25, 17.82, 17.56, -0.26. HRMS-ESI (rn/z)calculated value C13H180SiNa [M+Nat 241.1019, measuredvalue 241.1025.
2-(2-trimethylsilylethynyl)-3,4-(o-carborano)-2,5-dihydrofuran[ No CAS ]
Yield
Reaction Conditions
Operation in experiment
51%
A solution of 1-bromomethyl--carborane (1) (1.51 g,6.36 mmol) in THF (5 mL) was added dropwise to lithium diisopropylamide (prepared from 1.6 M solution of butyllithium in hexane (4.3 mL) and diisopropylamine (0.91 mL) in THF(10 mL)) at -78 C. The resulting solution was stirred for 1 h at-78 C, which was accompanied by the formation of a white precipitate. Then, 3-trimethylsilylprop-2-ynal (0.88 g, 7 mmol)was added to the mixture at -78 C, which was stirred for 30 min, raising the temperature to ambient. The reaction mixture was poured into 1 HCl (25 mL), the organic phase was separated, the aqueous phase was extracted with diethyl ether (10 mL). The combined organic extracts were dried with Na2SO4. The solvent was evaporated, the residue was recrystallized from methanol (5 mL). The yield was 0.92 g (3.25 mmol, 51%), colorless crystals. Found (%): C, 37.86; H, 7.81. C9H22B10OSi. Calculated (%):, 38.27; , 7.85. 1H NMR (CDCl3), : 5.13 (s, 1 H, CHO);4.38 (d, 1 H, HCHO, J = 8.6 Hz); 4.26 (d, 1 H, HCHO,J = 8.8 Hz); 3.13-1.47 (br.m, 10 H, BH); 0.24 (s, 9 H, CH3Si).13C NMR (CDCl3), : 97.6 (HCC?C); 95.6 (C?CSi); 80.3(Ccarb); 78.5 (Ccarb); 73.5(CHO); 73.0 (CH2O); 0.5 (CSi).11B NMR (CDCl3), : -5.8 (d, 2 B, J = 166 Hz); -7.6 (d, 1 B,J = 148 Hz); -8.2 (d, 2 B, J = 160 Hz); -10.2 (d, 1 B); -12.4(d, 2 B, J = 159 Hz); -13.2 (d, 2 B, J = 175 Hz).
With potassium carbonate; In dichloromethane; at 20℃; for 3h;
General procedure: A mixture of ynal 1 (0.5 mmol), amidine hydrochloride 2 (0.6 mmol), K2CO3(1.0 mmol), and MCM-41-PPh3-AuCl (41 mg, 0.015 mmol) in DCM (3mL) was stirred at room temperature for 3 h (TLC monitored). The resulting mixture was then diluted with ethyl acetate (15 mL) and filtered. The gold catalyst was washed with distilled water(5 mL), and dry ethanol (25mL) and reused in the next run. The filtrate was concentrated under reduced pressure and the residue was purified by chromatography on silicagel (eluent: petroleum ether/ethyl acetate) to afford the desired product 3.
With potassium carbonate; In dichloromethane; at 20℃; for 3h;
General procedure: A mixture of ynal 1 (0.5 mmol), amidine hydrochloride 2 (0.6 mmol), K2CO3(1.0 mmol), and MCM-41-PPh3-AuCl (41 mg, 0.015 mmol) in DCM (3mL) was stirred at room temperature for 3 h (TLC monitored). The resulting mixture was then diluted with ethyl acetate (15 mL) and filtered. The gold catalyst was washed with distilled water(5 mL), and dry ethanol (25mL) and reused in the next run. The filtrate was concentrated under reduced pressure and the residue was purified by chromatography on silicagel (eluent: petroleum ether/ethyl acetate) to afford the desired product 3.
With potassium carbonate; In dichloromethane; at 20℃; for 3h;
General procedure: A mixture of ynal 1 (0.5 mmol), amidine hydrochloride 2 (0.6 mmol), K2CO3(1.0 mmol), and MCM-41-PPh3-AuCl (41 mg, 0.015 mmol) in DCM (3mL) was stirred at room temperature for 3 h (TLC monitored). The resulting mixture was then diluted with ethyl acetate (15 mL) and filtered. The gold catalyst was washed with distilled water(5 mL), and dry ethanol (25mL) and reused in the next run. The filtrate was concentrated under reduced pressure and the residue was purified by chromatography on silicagel (eluent: petroleum ether/ethyl acetate) to afford the desired product 3.
With potassium carbonate; In dichloromethane; at 20℃; for 3h;
General procedure: A mixture of ynal 1 (0.5 mmol), amidine hydrochloride 2 (0.6 mmol), K2CO3(1.0 mmol), and MCM-41-PPh3-AuCl (41 mg, 0.015 mmol) in DCM (3mL) was stirred at room temperature for 3 h (TLC monitored). The resulting mixture was then diluted with ethyl acetate (15 mL) and filtered. The gold catalyst was washed with distilled water(5 mL), and dry ethanol (25mL) and reused in the next run. The filtrate was concentrated under reduced pressure and the residue was purified by chromatography on silicagel (eluent: petroleum ether/ethyl acetate) to afford the desired product 3.
(3S)-2-(bromomethyl)-3,7-dimethylocta-1,6-diene[ No CAS ]
(6S)-6,10-dimethyl-5-methylene-1-(trimethylsilyl)undec-9-en-1-yn-3-ol[ No CAS ]
Yield
Reaction Conditions
Operation in experiment
72%
To a suspension of zinc granular (9.98 g, 0.15 mol) in THF (54 mL) was addeddibromoethane (1 mL). The mixture was stirred at 65C for 1 min then cooled toroomed temperature. TMSCl (1.1 mL) was then added and the mixture wasstirred at room temperature for 15 min. A solution of compound (S)-7 (14.1 g,0.061 mol) in THF (76 mL) was then added and the mixture was stirred at 45C for1 hr. After cooling to 0C, a solution of 3-(trimethylsilyl)propiolaldehyde 8 (6.99 g,0.055 mol) in THF (150 mL) was added via syringe pump over 1 hr. Once the addition complete, thereaction was quenched with MeOH/H2O 1:1 (80 mL), water was added and the mixture was extractedwith 3x100 mL of Et2O. The combined organic layers were washed with aqueous NaOH solution,dried over MgSO4, filtered and concentrated in vacuo. The crude was purified by flashchromatography (cyclohexane/DCM 60:40 to 40:60) to give a mixture of isomers as a colorless oil(11.18 g, 72%). This step has been conducted on 3 batches. 1H NMR (300 MHz, CDCl3) delta 5.11-5.05 (m,1H), 4.93 (s, 1H), 4.92 (d, J= 0.9Hz, 1H), 4.50-4.46 (m, 1H), 2.42 (d, J=6.6 Hz, 2H), 2.16 (sext, J=6.9 Hz,1H), 2.05 (brs, 1H), 1.93 (q, J=7.5 Hz, 2H), 1.67 (s, 3H), 1.58 (s, 3H), 1.54-1.42 (m, 1H), 1.34-1.25 (m,1H), 1.03 (d, J=6.9 Hz, 3H), 0.16 (s, 9H); 13C NMR (75mHz, CDCl3) delta 149.8, 149.7, 131.6, 124.6, 111.6,106.5, 89.5, 61.4, 61.3, 42.9, 42.8, 39.4, 39.2, 35.8, 35.8, 26.0, 25.9, 25.8, 20.0, 19.9, 17.8, -0.1.
ethyl (E)-2-cinnamyl-5-(trimethylsilyl)pent-2-en-4-enoic acid[ No CAS ]
Yield
Reaction Conditions
Operation in experiment
78%
This example is the same as Example 3 above, except that in a 200 mL Shrek tube, under an argon atmosphere, add (E)-3-phenylprop-2-en-1-ol (6 mmol), ethyl 2-(triphenyl-1,5-phosphoryl)acetate (5 mmol), barium bis(trifluoromethylsulfonyl)imide (5mol%), [1,1'-Bis(diphenylphosphine)ferrocene]palladium dichloromethane complex (3 mol%) in dimethyl sulfoxide (30 mL), the reaction was stirred at 100 C, and the reaction was carried out After 48h, to the reaction mixture was added 3-(trimethylsilyl)propynal (6 mmol),Continue to react at room temperature for 12h. After the reaction was completed, the reaction mixture was subjected to liquid separation extraction with ethyl acetate and saturated saline solution. After drying, the ethyl acetate was distilled off under reduced pressure, and petroleum ether and ethyl acetate (PE / EA = 100: 1) were used for column chromatography. )the residue was purified to obtain 1.22 g of gram-grade reaction product (E)-2-cinnamyl-5-(trimethylsilyl)pent-2-en-4-ynyl ethyl ester in a yield of 78%.
(3) Compound 4b (0.72 mmol, 190 mg), anhydrous calcium chloride (400 mg), tetrahydrofuran (10 mL), 3-<strong>[2975-46-4]trimethylsilylpropynal</strong> (1.08 mmol, 140 mg), p-toluene Sulfonic acid (0.22 mmol, 37 mg) was sequentially added to a 50 mL round-bottomed flask, and the mixture was reacted at room temperature for 3 h. The reaction was complete (TLC monitoring reaction, developing solvent: DCM), and then DDQ ( 0.79 mmol, 180 mg), reaction for 20 min, the solvent was removed under reduced pressure, and the obtained crude product was purified by silica gel column chromatography (eluent: DCM)170 mg of white solid compound 5b was obtained (64% yield).
(3) Compound 4c (1.22 mmol, 350 mg), anhydrous magnesium sulfate (700 mg), tetrahydrofuran (30 mL), 3-<strong>[2975-46-4]trimethylsilylpropynal</strong> (1.83 mmol, 230 mg), concentrated sulfuric acid (0.37 mmol, 36 mg) was sequentially added to a 100 mL round-bottomed flask. The mixture was reacted at room temperature for 3 h, and the reaction was complete. Then, DDQ (1.34 mmol, 304.63 mg) was added in an ice-water bath, and the reaction was carried out for 20 min. SolventThe crude product obtained was purified by silica gel column chromatography (eluent: DCM) to give 259 mg of compound 5c as a white solid (yield 54%).
(3) Compound 4d (1.84 mmol, 500 mg), anhydrous sodium sulfate (1000 mg), tetrahydrofuran (30 mL), 3-<strong>[2975-46-4]trimethylsilylpropynal</strong> (2.76 mmol, 347 mg), p-toluene Sulfonic acid (0.55 mmol, 95 mg) was sequentially added to a 100 mL round-bottomed flask. The mixture was reacted at room temperature for 3 h, and the reaction was complete. Then, DDQ (2.02 mmol, 460 mg) was added in an ice-water bath, and the reaction was carried out for 20 min. The solvent was removed, and the obtained crude product was purified by silica gel column chromatography (eluent: DCM).This gave 348 mg of compound 5d as a white solid (65% yield).
(3) Compound 4e (1.04 mmol, 323.5 mg), anhydrous copper sulfate (647 mg),Tetrahydrofuran (30 mL),3-<strong>[2975-46-4]trimethylsilylpropynal</strong> (1.46 mmol, 184 mg),P-Toluenesulfonic acid (0.31 mmol, 54 mg) was sequentially added to a 100 mL round bottom flask.The mixture was reacted at room temperature for 3 h.Then add DDQ (1.14 mmol, 260mg) in an ice-water bath and react for 20 min. The solvent was removed under reduced pressure.The crude product was purified by silica gel column chromatography (eluent: DCM) to obtain 173 mg5e (yield 40%) as a white solid.
(4) Compound 5f (2.53 mmol, 700 mg), anhydrous magnesium sulfate (1400 mg), THF (30 mL), 3-<strong>[2975-46-4]trimethylsilylpropynal</strong> (3.79 mmol, 479 mg),Concentrated sulfuric acid (0.76 mmol, 74 mg) was sequentially added to a 100 mL round bottom flask.The mixture was reacted at room temperature for 3 h.The reaction was complete. DDQ (2.78 mmol, 632mg) was added in an ice-water bath, and the reaction was carried out for 20 min. The solvent was removed under reduced pressure.The crude product was purified by silica gel column chromatography (eluent: DCM)411.5 mg of white solid compound 6f was obtained (yield 43%).
2-amino-N-(2-(hydroxymethyl)-4-methoxyphenyl)benzamide[ No CAS ]
C21H22N2O3Si[ No CAS ]
Yield
Reaction Conditions
Operation in experiment
48%
(4) Compound 5g (2.83 mmol, 770 mg),Anhydrous sodium sulfate (1600 mg), THF (30 mL),3-<strong>[2975-46-4]trimethylsilylpropynal</strong> (4.12 mmol, 518.6 mg),P-Toluenesulfonic acid (0.88 mmol, 151.7 mg) was sequentially added to a 100 mL round bottom flask.The mixture was reacted at room temperature for 3 h.The reaction was complete. DDQ (3.23 mmol, 734 mg) was added in an ice-water bath, and the reaction was carried out for 20 min. The solvent was removed under reduced pressure.The crude product was purified by silica gel column chromatography (eluent: DCM)6 g (48% yield) of 394 mg of a white solid compound was obtained.
(3) Compound 4i (2.16 mmol, 688 mg), anhydrous sodium sulfate (1400 mg), THF (30 mL), 3-<strong>[2975-46-4]trimethylsilylpropynal</strong> (3.02 mmol, 381.48) mg) and concentrated hydrochloric acid (0.648 mmol, 64) were sequentially added to a 250 mL round bottom flask. The mixture was reacted at room temperature for 3 h. The reaction was complete. DDQ (2.38 mmol, 540.10 mg) was added in an ice-water bath and the reaction was carried out for 20 min The solvent was removed under reduced pressure, and the obtained crude product was purified by silica gel column chromatography (eluent: DCM) to obtain 319.8 mg of a white solid compound 5i (yield 35%).
(3) Under electromagnetic stirring, compound 4j (2.22 mmol, 600 mg), anhydrous chlorination (1200 mg), THF (30 mL), 3-<strong>[2975-46-4]trimethylsilylpropynal</strong> (3.1 mmol, 391 mg), p-toluenesulfonic acid (0.66 mmol, 115 mg) were sequentially added to a 100 mL round bottom flask, and the mixture was reacted at room temperature for 3 h. The reaction was complete. DDQ (2.44 mmol, 554 mg) was added in an ice water bath. The reaction was carried out for 20 min. The solvent was removed under reduced pressure, and the obtained crude product was purified by silica gel column chromatography (eluent: DCM) to obtain 363 mg of a white solid compound 5j (yield 40%).
(3) Under electromagnetic stirring, compound 4a (2.53 mmol, 700 mg), anhydrous sodium sulfate (1400 mg), tetrahydrofuran (20 mL), 3-<strong>[2975-46-4]trimethylsilylpropynal</strong> (3.54 mmol, 446 mg) and p-toluenesulfonic acid (0.76 mmol, 130 mg) were sequentially added to a 250 mL round bottom flask, and the mixture was reacted at room temperature for 3 h.Then add DDQ (2.78 mmol, 632 mg) in an ice-water bath, react for 20 min, remove the solvent under reduced pressure,The crude product obtained was purified by silica gel column chromatography (eluent: DCM)410 mg of compound 5a was obtained as a white solid (73% yield).
(2) Compound 3m (5.15 mmol, 1000 mg), anhydrous calcium sulfate (2000 mg), THF (40 mL),3-Trimethylsilylpropynal (7.21 mmol, 908 mg) and p-toluenesulfonic acid (1.5 mmol, 274 mg) were sequentially added to a 250 mL round bottom flask, and the mixture was reacted at room temperature for 3 h. The reaction was complete DDQ (5.71 mmol, 1296 mg) was added in an ice water bath, and the reaction was carried out for 20 min. The solvent was removed under reduced pressure.The crude product obtained was purified by silica gel column chromatography (eluent: DCM)778.2 mg of white compound 4m was obtained (yield 50%).
(3) Under electromagnetic stirring, compound 4n (1.90 mmol, 647 mg), anhydrous copper sulfate (1300 mg), THF (30 mL), 3-<strong>[2975-46-4]trimethylsilylpropynal</strong> (2.65 mmol, 334 mg) and concentrated hydrochloric acid (0.57 mmol, 56 mg) were sequentially added to a 250 mL round bottom flask. The mixture was reacted at room temperature for 3 h. The reaction was complete. DDQ (2.09 mmol, 473 mg) was added in an ice-water bath, and the reaction was carried out for 20 min. Remove the solvent under reduced pressure,The crude product obtained was purified by silica gel column chromatography (eluent: DCM)364 mg of compound 5n was obtained as a white solid (yield 43%)
(2) Compound 3o (2.19 mmol, 500 mg), magnesium sulfate (1000 mg), THF (30mL), 3-<strong>[2975-46-4]trimethylsilylpropynal</strong> (3.07 mmol, 387 mg), P-Toluenesulfonic acid (0.66 mmol, 113 mg) was sequentially added to a 100 mL round-bottomed flask. The mixture was reacted at room temperature for 3 h. The reaction was complete. DDQ (2.41 mmol, 547 mg) was added in an ice-water bath, and the reaction was carried out for 20 min. The solvent was removed under reduced pressure, and the obtained crude product was purified by silica gel column chromatography (eluent: DCM) to obtain 709.8 mg of a white solid compound 4o (yield 97%).
3-(1-oxo-4-[[3-(trimethylsilyl)prop-2-yn-1-yl]amino]-2,3-dihydro-1H-isoindol-2-yl)piperidine-2,6-dione[ No CAS ]
Yield
Reaction Conditions
Operation in experiment
80%
Stage #1: 3-(trimethylsilyl)prop-2-yn-1-al; Lenalidomide With acetic acid In dichloromethane at 40℃; for 1h;
Stage #2: With sodium tris(acetoxy)borohydride In dichloromethane at 35℃; for 16h;
1 Step 1
Into a 100-mL round-bottom flask, was placed 3-(4-amino-l-oxo-2,3-dihydro-lH- isoindol-2-yl)piperidine-2,6-dione (1.0 g, 3.86 mmol, 1.0 equiv), 3 -(trimethyl silyl)prop-2-ynal (486 mg, 3.85 mmol, 1.0 equiv) in dichloromethane (30 mL). This was followed by the addition of HOAc (5.0 mL), and the reaction mixture was stirred at 40 °C for 1 hr. To this was addedNaBH(OAc)3(3.3 g, 15.57 mmol, 4.0 equiv). The resulting solution was stirred for another 16 hr at 35°C in an oil bath. The resulting solution was extracted with dichloromethane (100 mL x 2). The resulting mixture was washed with brine (50 mL x 2) and concentrated. This resulted in 1.14 g (80%) of 3-(l-oxo-4-[[3-(trimethylsilyl)prop-2-yn-l-yl]amino]-2,3-dihydro-lH-isoindol-2- yl)piperidine-2,6-dione as a white solid.
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