Name: 35573-93-4|3-Chloropropionaldehydediethylacetal|95% (stabilized with K2CO3)
Brand: Ambeed
SKU: A1263026
Price: 9.0 USD
Availability: InStock
Rating: 93 (22 reviews)

1
[ 35573-93-4 ]
[ 16777-87-0 ]

Reference： [1]Chemische Berichte,1900,vol. 33,p. 2763
[2]Journal of the Chemical Society,1941,p. 406

2
[ 35573-93-4 ]
[ 3054-95-3 ]

Yield	Reaction Conditions	Operation in experiment
	With potassium hydroxide
	With alkali
	With potassium <i>tert</i>-butylate

With alkali Darst_.;

Reference： [1]Wohl [Chemische Berichte, 1898, vol. 31, p. 1799]
[2]Hersant; Linnell [Quarterly Journal of Pharmacy and Pharmacology, 1931, vol. 4, p. 62,86][Chemisches Zentralblatt, 1932, vol. 103, # I, p. 2160]
[3]Rothstein [Journal of the Chemical Society, 1940, p. 1563]
[4]Wohl [Chemische Berichte, 1898, vol. 31, p. 1799] Witzemann [Journal of the American Chemical Society, 1914, vol. 36, p. 1909] Reeves [Journal of the Chemical Society, 1927, p. 2481] Evans; Hass [Journal of the American Chemical Society, 1926, vol. 48, p. 2705] Witzemann et al. [Organic Syntheses, 1931, vol. 11, p. 1]
[5]Wohl [Chemische Berichte, 1898, vol. 31, p. 1799] Witzemann [Journal of the American Chemical Society, 1914, vol. 36, p. 1909]

3
[ 35573-93-4 ]
[ 41365-75-7 ]

Yield	Reaction Conditions	Operation in experiment
	With ethanol; ammonia
	With sodium azide; hydrogen 1.) DMF, 2.) C₂H₅OH, 4 d; Yield given. Multistep reaction;
	Multi-step reaction with 2 steps 1: NaN₃ / dimethylsulfoxide / 16 h / 50 °C 2: 8.2 g / H₂ / 5 percent Pd/C / methanol / 2 h / 20 °C / 2585.74 Torr

Multi-step reaction with 2 steps 1: 83 percent / dimethylformamide / 5 h / 145 °C 2: 87 percent / hydrazine / methanol / 2 h / Heating

Reference： [1]Albers et al. [Chemische Berichte, 1944, vol. 77/79, p. 617,626]
[2]Durrwachter, John R.; Wong, Chi-Huey [Journal of Organic Chemistry, 1988, vol. 53, # 18, p. 4175 - 4181]
[3]Xun, Jin; Huang, Haidong; Vogel, Kurt W.; Drueckhammer, Dale G. [Bioorganic Chemistry, 2005, vol. 33, # 2, p. 90 - 107]
[4]Carroll; Berrang; Linn [Journal of Heterocyclic Chemistry, 1981, vol. 18, # 5, p. 941 - 946]

4
[ 64-17-5 ]
[ 107-02-8 ]
[ 35573-93-4 ]

Yield	Reaction Conditions	Operation in experiment
90%	With hydrogenchloride; calcium chloride at 0℃; for 24h;
	With hydrogenchloride
	With hydrogenchloride

Reference： [1]Wang, Hui-Po; Lee, On; Fan, Chin-Tsai; Lee, Lain-Tze [Journal of the Chinese Chemical Society, 1995, vol. 42, # 3, p. 569 - 572]
[2]Kuffner,F. et al. [Monatshefte fur Chemie, 1960, vol. 91, p. 1152 - 1161] Wohl [Chemische Berichte, 1898, vol. 31, p. 1799] Alsberg [Jahresbericht ueber die Fortschritte der Chemie und Verwandter Theile Anderer Wissenschaften, 1864, p. 495] Wohl; Emmerich [Chemische Berichte, 1900, vol. 33, p. 2763]
[3]Barluenga, Jose; Fernandez, Jose R.; Yus, Miguel [Journal of the Chemical Society. Chemical communications, 1987, # 20, p. 1534 - 1535]

5
[ 35573-93-4 ]
[ 141-97-9 ]
[ 14499-62-8 ]

Yield	Reaction Conditions	Operation in experiment
42%	With potassium carbonate In dimethyl sulfoxide at 100 - 120℃; for 15h;	General procedure for the alkylation of methylene-active compounds. General procedure: Halo acetal 2a or 2b, 0.25 mol, was added with stirring to a mixture of 0.25 mol of the corresponding CH acid and 28 g (0.2 mol) of calcined potassium carbonate in 100 mL of DMSO. The mixture was stirred for 15 h at 70- 80°C (in the reactions with 2a), or at 100-120°C (2b), cooled, and treated with water and diethyl ether (2 100 mL). The combined extracts were dried over anhydrous sodium sulfate, the solvent was distilled off, and the residue was distilled under reduced pressure.
	(i) NaH, benzene, DMF, (ii) /BRN= 1698609/, KI; Multistep reaction;

Reference： [1]Ismailov; Yusubov; Sadykhova; Gasymov; Ibragimova; Mamedov [Russian Journal of Organic Chemistry, 2016, vol. 52, # 10, p. 1390 - 1393][Zh. Org. Khim., 2016, vol. 52, # 10, p. 1390 - 1393,4]
[2]Brenner,J.E. [Journal of Organic Chemistry, 1961, vol. 26, p. 22 - 27]

6
[ 35573-93-4 ]
[ 109-89-7 ]
[ 3616-60-2 ]

Yield	Reaction Conditions	Operation in experiment
63.2%	With potassium carbonate In acetone at 60℃; for 12h;

Reference： [1]Location in patent: experimental part Gazizov; Burilov; Pudovik; Konovalov [Russian Journal of General Chemistry, 2008, vol. 78, # 12, p. 2409 - 2410]
[2]Julia,M.; Tilly,G. [Bulletin de la Societe Chimique de France, 1965, p. 2175 - 2182]

7
[ 35573-93-4 ]
[ 58422-60-9 ]
[ 145611-10-5 ]

Reference： [1]Collection of Czechoslovak Chemical Communications,1992,vol. 57,p. 1967 - 1981

8
[ 35573-93-4 ]
[ 51632-12-3 ]
2-(4-Bromo-phenyl)-5,5-diethoxy-2-isopropyl-pentanenitrile [ No CAS ]

Reference： [1]Chemical and Pharmaceutical Bulletin,1988,vol. 36,p. 4103 - 4120

9
[ 35573-93-4 ]
[ 20850-49-1 ]
[ 27339-24-8 ]

Yield	Reaction Conditions	Operation in experiment
70%	With sodium amide In toluene for 5h; Heating;
	With sodium amide In toluene for 3h; Heating / reflux;	4.a Preparation of Verapamil from N-Methyl-3,4-dimethoxyphenylethylamine and Salt Thereof of Formula 6 According to U.S. Pat. No. 4,115,432 Example 1 (a) 573 g (2.62 mol) of α-isopropyl veratryl cyanide and 481 g (1.12.62 mol) of β-chloropropionaldehyde diethyl acetal were dissolved in 2.7 l of dry toluene with heating. 393 g of a 30 percent sodium amide suspension in toluene (117.6 g or 1.152.62 mol of NaNH2) were added drop wise to the boiling solution with vigorous stirring during the course of an hour. After 3 hours the reaction solution was cooled and washed once with 3 l of an ice-water mixture and subsequently washed twice with 1 l of water. The toluene phase was dried and concentrated. Distillation of the residue gives 772 g of α-isopropyl-α-(γ-diethoxypropyl)-veratryl cyanide.

Reference： [1]Butora, Gabriel; Blaha, Ludvik; Rajsner, Miroslav; Helfert, Ivan [Collection of Czechoslovak Chemical Communications, 1992, vol. 57, # 9, p. 1967 - 1981]
[2]Current Patent Assignee: TEVA PHARMACEUTICAL INDUSTRIES LTD. - US2009/171110, 2009, A1 Location in patent: Page/Page column 6

10
[ 35573-93-4 ]
[ 23037-61-8 ]
[ 79842-27-6 ]

Yield	Reaction Conditions	Operation in experiment
84%	With tetrafluoroboric acid-diethyl ether complex In nitromethane for 1.3h;

Reference： [1]McCall, J. M.; McCall, R. B.; TenBrink, R. E.; Kamdar, B. V.; Humphrey, S. J.; et al. [Journal of Medicinal Chemistry, 1982, vol. 25, # 1, p. 75 - 81]

11
[ 35573-93-4 ]
[ 1216963-74-4 ]
[ 68654-84-2 ]

Yield	Reaction Conditions	Operation in experiment
91%	In dimethyl sulfoxide at 15℃; for 3h;

Reference： [1]Johnson, William S.; Yarnell, Thomas M.; Myers, Robert F.; Morton, Douglas R.; Boots, Sharon G. [Journal of Organic Chemistry, 1980, vol. 45, # 7, p. 1254 - 1259]

12
[ 35573-93-4 ]
[ 81903-99-3 ]
2-(3-Chloro-1-ethoxy-propyl)-2-ethyl-cyclopentanone [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
70%	With titanium tetrachloride In diethyl ether at -78℃; for 3h;

Reference： [1]Overman, Larry E.; Sworin, Michael; Bass, Lawrence S.; Clardy, Jon [Tetrahedron, 1981, vol. 37, # 23, p. 4041 - 4045]

13
[ 35573-93-4 ]
[ 70822-01-4 ]
[ 70822-39-8 ]

Yield	Reaction Conditions	Operation in experiment
84%	With tetrafluoroboric acid-diethyl ether complex In nitromethane at 22℃; for 3h;

Reference： [1]McCall, J. M.; McCall, R. B.; TenBrink, R. E.; Kamdar, B. V.; Humphrey, S. J.; et al. [Journal of Medicinal Chemistry, 1982, vol. 25, # 1, p. 75 - 81]

14
[ 35573-93-4 ]
[ 4744-08-5 ]

Yield	Reaction Conditions	Operation in experiment
	With water; naphthalen-1-yl-lithium 1.) THF, -78 deg C, 6 h, 2.) 20 deg C, 2 h; Yield given. Multistep reaction;
	Multi-step reaction with 2 steps 1: lithium naphthalenide / tetrahydrofuran / 6 h / -78 °C 2: 80 percent / H₂O / tetrahydrofuran / 2 h / -78 - 20 °C / also other electrophiles (D₂O, (PhCH₂)2S₂, n-C₃H₇CHO, PhCHO, n-C₇H₁₅CHO, PhCH=NPh)

Reference： [1]Barluenga, Jose; Fernandez, Jose R.; Rubiera, Covadonga; Yus, Miguel [Journal of the Chemical Society. Perkin transactions I, 1988, p. 3113 - 3118]
[2]Barluenga, Jose; Rubiera, Covadonga; Fernandez, Jose R.; Yus, Miguel [Journal of the Chemical Society. Chemical communications, 1987, # 6, p. 425 - 426]

15
[ 35573-93-4 ]
[ 5930-92-7 ]
[ 150368-01-7 ]

Reference： [1]Journal of the American Chemical Society,1993,vol. 115,p. 7061 - 7071

16
[ 35573-93-4 ]
[ 140-29-4 ]
[ 93722-30-6 ]

Yield	Reaction Conditions	Operation in experiment
87%	Stage #1: phenylacetonitrile With lithium diisopropyl amide In tetrahydrofuran at -78℃; for 0.666667h; Stage #2: 3-chloro-1,1-diethoxy-propane In tetrahydrofuran at -78℃; Cooling;
80%	With sodium hydride In N,N-dimethyl-formamide at 70℃; for 2h;

Reference： [1]Pitta, Bhaskar Reddy; Fleming, Fraser F. [Organic Letters, 2010, vol. 12, # 12, p. 2810 - 2813]
[2]King, Frank D. [Journal of the Chemical Society. Perkin transactions I, 1986, p. 447 - 454]

17
[ 35573-93-4 ]
[ 123-72-8 ]
[ 105-21-5 ]

Reference： [1]Journal of the Chemical Society. Perkin transactions I,1988,p. 3113 - 3118

18
[ 35573-93-4 ]
[ 108-98-5 ]
[ 89593-89-5 ]

Yield	Reaction Conditions	Operation in experiment
81%	With hydrogenchloride
	With hydrogenchloride In chloroform at 20℃; for 24h;
	With hydrogenchloride

Reference： [1]Wang, Lihong; Prabhudas, Bodhuri; Clive, Derrick L. J. [Journal of the American Chemical Society, 2009, vol. 131, p. 6003 - 6012]
[2]Benedetti, Fabio; Stirling, Charles J.M. [Journal of the Chemical Society. Perkin transactions II, 1986, p. 605 - 612]
[3]Benedetti, Fabio; Stirling, Charles J. M. [Journal of the Chemical Society. Chemical communications, 1983, # 22, p. 1374 - 1376]

19
[ 35573-93-4 ]
[ 105-56-6 ]
[ 118252-48-5 ]

Yield	Reaction Conditions	Operation in experiment
	With sodium methylate; sodium iodide 1.) EtOH, 2.) DMF, steam bath, 5 h; Yield given. Multistep reaction;
	With sodium methylate In <i>N</i>-methyl-acetamide; (2S)-N-methyl-1-phenylpropan-2-amine hydrate; ethanol	1.a (a) (a) Preparation of ethyl 2-cyano-5,5-diethoxypentanoate To a stirred solution of 16.2 g (0.30 mol) of sodium methoxide in 100 ml of absolute ethanol was added 160 ml (170 g, 1.50 mol) of ethyl cyanoacetate. The solution was spin evaporated in vacuo at 40° C. and the residual white solid was dissolved in 200 ml of dry dimethylformamide. To this solution was added 50 ml (50 g, 0.30 mol) of 3-chloropropionaldehyde diethyl acetal and a crystal of sodium iodide, and the solution was heated on a steam bath with magnetic stirring and protection from moisture for 5 hours. The red-brown solution was cooled, poured into 300 ml of ice water and extracted with diethylether (6200 ml). The organic phase was washed with water (350 ml), brine (50 ml) and dried over magnesium suphate. The solution was filtered, spin evaporated in vacuo, and the residue was distilled to give 41.3 g (57%) of a clear liquid, bp 90°-108° (0.05 mm Hg) which was sufficiently pure for the next step. Fractional distillation gave as a main fraction a clear liquid, bp 103°-108° (0.025 mm Hg); NMR (CDCl3) δ1.20 (t, 6H, CH(OCH2 CH3)2), 1.31 (t, 3H, CO2 CH2 CH3), 1.90 (m, 2H, CH2 CHCN), 3.60 (m, 5H, CH(OCH2 CH3)2 +CHCN), 4.24 (q, 2H, CO2 CH2), 4.51 (t, 1H, CH(OCH2)CH3); 1R (film) 2265, 1750, 1450 cm-1.
	With sodium methylate In <i>N</i>-methyl-acetamide; (2S)-N-methyl-1-phenylpropan-2-amine hydrate; ethanol	1.a (a) (a) Preparation of ethyl 2-cyano-5,5-diethoxypentanoate To a stirred solution of 16.2 g (0.30 mol) of sodium methoxide in 100 ml of absolute ethanol was added 160 ml (170 g, 1.50 mol) of ethyl cyanoacetate. The solution was spin evaporated in vacuo at 40° C. and the residual white solid was dissolved in 200 ml of dry dimethylformamide. To this solution was added 50 ml (50 g, 0.30 mol) of 3-chloropropionaldehyde diethyl acetal and a crystal of sodium iodide, and the solution was heated on a steam bath with magnetic stirring and protection from moisture for 5 hours. The red-brown solution was cooled, poured into 300 ml of ice water and extracted with diethylether (6200 ml). The organic phase was washed with water (350 ml), brine (50 ml) and dried over magnesium suphate. The solution was filtered, spin evaporated in vacuo, and the residue was distilled to give 41.3 g (57%) of a clear liquid, bp 90°-108° (0.05 mm Hg) which was sufficiently pure for the next step. Fractional distillation gave as a main fraction a clear liquid, bp 103°-108° (0.025 mm Hg); NMR (CDCl3)δ1.20 (t, 6H, CH(OCH2 CH3)2), 1.31 (t, 3H, CO2 CH2 CH3), 1.90 (m, 2H, CH2 CHCN), 3.60 (m, 5H, CH(OCH2 CH3)2 +CHCN), 4.24 (q, 2H, CO2 CH2), 4.51 (t, 1H, CH(OCH2)CH3); 1R (film) 2265, 1750, 1450 cm-1.

Reference： [1]Kelley; McLean; Cohn; Edelstein; Duch; Smith; Hanlon; Ferone [Journal of Medicinal Chemistry, 1990, vol. 33, # 2, p. 561 - 567]
[2]Current Patent Assignee: GLAXOSMITHKLINE PLC - US4940713, 1990, A
[3]Current Patent Assignee: GLAXOSMITHKLINE PLC - US4880812, 1989, A

20
[ 35573-93-4 ]
[ 100-51-6 ]
[ 78314-63-3 ]

Yield	Reaction Conditions	Operation in experiment
71%	With sodium hydroxide; tetrabutyl hydrogen sulfate In water; sodium chloride 60 deg C, 12 h, then 100 deg C, 48 h;
	With sodium hydroxide; Bu₄N*H₂SO₄

Reference： [1]Yamaura; Suzuki; Hashimoto; et al. [Bulletin of the Chemical Society of Japan, 1985, vol. 58, # 10, p. 2812 - 2820]
[2]Wakamiya, Tateaki; Konishi, Kunikazu; Chaki, Haruyuki; Teshima, Tadashi; Shiba, Tetsuo [Heterocycles, 1981, vol. 15, # 2, p. 999 - 1005]

21
[ 35573-93-4 ]
[ 17242-85-2 ]
[ 133625-58-8 ]

Yield	Reaction Conditions	Operation in experiment
91%	With trimethylsilyl trifluoromethanesulfonate In dichloromethane at -30℃;

Reference： [1]Tietze, Lutz F.; Krach, Thomas; Beller, Matthias; Arlt, Michael [Chemische Berichte, 1991, vol. 124, # 9, p. 2019 - 2024]

22
[ 35573-93-4 ]
[ 51089-83-9 ]
[ 161690-40-0 ]

Yield	Reaction Conditions	Operation in experiment
87%	With Montmorillonite K-10 clay; trifluoroacetic acid In dichloromethane
87%	With Montmorillonite K-10 clay; trifluoroacetic acid In dichloromethane for 5h; Ambient temperature;

Reference： [1]Lee, David A.; Brisson, Jean M.; Smith, Kevin M. [Heterocycles, 1995, vol. 40, # 1, p. 131 - 136]
[2]Lee, David A.; Smith, Kevin M. [Journal of the Chemical Society. Perkin transactions I, 1997, # 8, p. 1215 - 1227]

23
[ 35573-93-4 ]
[ 135746-47-3 ]
[ 162318-00-5 ]

Yield	Reaction Conditions	Operation in experiment
96%	With n-butyllithium In tetrahydrofuran; hexane 1.) -25 deg C, 2.5 h, 2.) -25 deg C, 4 h;

Reference： [1]Molander, Gary A.; Siedem, Christopher S. [Journal of Organic Chemistry, 1995, vol. 60, # 1, p. 130 - 138]

24
[ 150-19-6 ]
[ 35573-93-4 ]
[ 153750-80-2 ]

Yield	Reaction Conditions	Operation in experiment
91%	With sodium hydroxide In water 1.) room temperature, 30 min, 2.) reflux, 15 h;
47%	Stage #1: O-methylresorcine With sodium hydroxide In water for 0.5h; Stage #2: 3-chloro-1,1-diethoxy-propane In water for 16h; Reflux;	1-(3,3-diethoxypropoxy)-3-methoxybenzene To a solution of NaOH (1.36 g, 34 mmol) in H2O (5 mL), 3-methoxyphenol (3.01 g, 24 mmol) was added. The mixture was stirred for 30 minutes then 3-chloro-1,1-diethoxypropane (2.02 g, 12 mmol) was added. The solution was refluxed for 16 hours then cooled to room temperature and neutralized with acetic acid. The neutral solution was extracted with Et2O then dried over Na2SO4. The crude oil was purified using column chromatography. 1.46 g (47%); clear oil; 1H NMR (600 MHz, CDCl3): δ 7.17 (t, J = 8.1 Hz, 1H), 6.47 (m, 3H), 4.76 (t, J = 5.7 Hz, 1H), 4.03 (t, J = 6.3 Hz, 2H), 3.78 (s, 3H), 3.73-3.67 (m, 2H), 3.56-3.50 (m, 2H), 2.08 (m, 2H), 1.21 (t, J = 7.1 Hz, 6H).

Reference： [1]Cao, Zhisong; Liehr, Joachim G. [Synthetic Communications, 1996, vol. 26, # 6, p. 1233 - 1245]
[2]Stokes, Sean; Mustain, Rachel; Pickle, Lydia; Mead, Keith T. [Tetrahedron Letters, 2012, vol. 53, # 30, p. 3890 - 3893]

25
[ 35573-93-4 ]
diluted NaOH-solution [ No CAS ]
[ 16777-87-0 ]

Reference： [1]Chemische Berichte,1900,vol. 33,p. 2763

26
[ 35573-93-4 ]
[ 3975-12-0 ]

Yield	Reaction Conditions	Operation in experiment
72%	Stage #1: 3-chloro-1,1-diethoxy-propane With naphthalene; lithium In tetrahydrofuran Stage #2: With copper dichloride In tetrahydrofuran at -78℃; for 0.75h; Stage #3: With ammonium chloride In tetrahydrofuran at -78 - 20℃;

Reference： [1]Pastor, Isidro M.; Yus, Miguel [Tetrahedron Letters, 2000, vol. 41, # 10, p. 1589 - 1592]

27
[ 106-39-8 ]
[ 35573-93-4 ]
[ 75677-02-0 ]

Reference： [1]European Journal of Organic Chemistry,2002,p. 1989 - 1995

28
[ 108-86-1 ]
[ 35573-93-4 ]
[ 104-53-0 ]

Yield	Reaction Conditions	Operation in experiment
51%	Stage #1: 3-chloro-1,1-diethoxy-propane With lithium In tetrahydrofuran at -78℃; for 1h; Stage #2: With zinc dibromide In tetrahydrofuran at -78 - 20℃; Stage #3: bromobenzene In tetrahydrofuran at 70℃; Further stages.;

Reference： [1]Yus, Miguel; Gomis, Joaquin [European Journal of Organic Chemistry, 2002, # 12, p. 1989 - 1995]

29
[ 35573-93-4 ]
[ 694-80-4 ]
[ 157433-36-8 ]

Yield	Reaction Conditions	Operation in experiment
19%	Stage #1: 3-chloro-1,1-diethoxy-propane With lithium In tetrahydrofuran at -78℃; for 1h; Stage #2: With zinc dibromide In tetrahydrofuran at -78 - 20℃; Stage #3: 2-bromo-1-chlorobenzene In tetrahydrofuran at 70℃; for 24h; Further stages.;

Reference： [1]Yus, Miguel; Gomis, Joaquin [European Journal of Organic Chemistry, 2002, # 12, p. 1989 - 1995]

30
[ 35573-93-4 ]
[ 99-90-1 ]
[ 150805-64-4 ]

Yield	Reaction Conditions	Operation in experiment
50%	Stage #1: 3-chloro-1,1-diethoxy-propane With lithium In tetrahydrofuran at -78℃; for 1h; Stage #2: With zinc dibromide In tetrahydrofuran at -78 - 20℃; Stage #3: para-bromoacetophenone In tetrahydrofuran at 70℃; Further stages.;

Reference： [1]Yus, Miguel; Gomis, Joaquin [European Journal of Organic Chemistry, 2002, # 12, p. 1989 - 1995]

31
[ 35573-93-4 ]
phenylmagnesium bromide [ No CAS ]
[ 6956-37-2 ]

Yield	Reaction Conditions	Operation in experiment
74%	With 1-methyl-pyrrolidin-2-one; palladium diacetate; tricyclohexylphosphine In tetrahydrofuran at 20℃; for 20h;

Reference： [1]Frisch, Anja C.; Shaikh, Nadim; Zapf, Alexander; Belier, Matthias [Angewandte Chemie - International Edition, 2002, vol. 41, # 21, p. 4056 - 4059]

32
[ 35573-93-4 ]
[ 688317-69-3 ]

Yield	Reaction Conditions	Operation in experiment
90%	With sodium azide In dimethyl sulfoxide at 50℃; for 16h;
88%	With sodium azide; potassium iodide In dimethyl sulfoxide at 20 - 90℃; Inert atmosphere;
	With sodium azide In dimethyl sulfoxide at 50℃; for 16h;

Reference： [1]Jokonya, Simbarashe; Langlais, Marvin; Leshabane, Meta; Reader, Paul W.; Vosloo, Johan A.; Pfukwa, Rueben; Coertzen, Dina; Birkholtz, Lyn-Marie; Rautenbach, Marina; Klumperman, Bert [Biomacromolecules, 2020, vol. 21, # 12, p. 5053 - 5066]
[2]Location in patent: experimental part Bellur, Esen; Yawer, Mirza A.; Hussain, Ibrar; Riahi, Abdolmajid; Fatunsin, Olumide; Fischer, Christine; Langer, Peter [Synthesis, 2009, # 2, p. 227 - 242]
[3]Xun, Jin; Huang, Haidong; Vogel, Kurt W.; Drueckhammer, Dale G. [Bioorganic Chemistry, 2005, vol. 33, # 2, p. 90 - 107]

33
[ 35573-93-4 ]
4-Amino-1-(3,3-diethoxy-propyl)-1H-pyrrole-2-carboxylic acid ethyl ester [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
	Multi-step reaction with 2 steps 1: 1.) K, 2.) KI / 1.) DMF, RT, 3 h, 2.) DMF, 100 deg C, 5 h 2: H₂ / 10percent Pd/C / methanol / 760 Torr / Ambient temperature

Reference： [1]He, Gong-Xin; Browne, Kenneth A.; Groppe, Jay C.; Blaskó, Andrei; Mei, Houng-Yau; Bruice, Thomas C. [Journal of the American Chemical Society, 1993, vol. 115, # 16, p. 7061 - 7071]

34
[ 35573-93-4 ]
[ 150368-04-0 ]

Yield	Reaction Conditions	Operation in experiment
	Multi-step reaction with 3 steps 1: 1.) K, 2.) KI / 1.) DMF, RT, 3 h, 2.) DMF, 100 deg C, 5 h 2: H₂ / 10percent Pd/C / methanol / 760 Torr / Ambient temperature 3: diethyl cyanophosphonate (DECP), Et₃N / tetrahydrofuran / 10 h / Ambient temperature

Reference： [1]He, Gong-Xin; Browne, Kenneth A.; Groppe, Jay C.; Blaskó, Andrei; Mei, Houng-Yau; Bruice, Thomas C. [Journal of the American Chemical Society, 1993, vol. 115, # 16, p. 7061 - 7071]

35
[ 35573-93-4 ]
1-(3,3-Diethoxy-propyl)-4-[(1-methyl-4-nitro-1H-pyrrole-2-carbonyl)-amino]-1H-pyrrole-2-carboxylic acid [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
	Multi-step reaction with 4 steps 1: 1.) K, 2.) KI / 1.) DMF, RT, 3 h, 2.) DMF, 100 deg C, 5 h 2: H₂ / 10percent Pd/C / methanol / 760 Torr / Ambient temperature 3: diethyl cyanophosphonate (DECP), Et₃N / tetrahydrofuran / 10 h / Ambient temperature 4: NaOH / ethanol; H₂O / 24 h / Heating

Reference： [1]He, Gong-Xin; Browne, Kenneth A.; Groppe, Jay C.; Blaskó, Andrei; Mei, Houng-Yau; Bruice, Thomas C. [Journal of the American Chemical Society, 1993, vol. 115, # 16, p. 7061 - 7071]

36
[ 35573-93-4 ]
[ 5182-44-5 ]
6-chloro-1-(2-chloroethyl)isochroman [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
	With hydrogenchloride;titanium tetrachloride; In nitromethane; dichloromethane;	A mixture of <strong>[5182-44-5]3-chlorophenethyl alcohol</strong> (XLV, 5.9055 g, 0.0398 mol), 3-chloropropionaldehyde diethyl acetal (LXII, 7.2 ml, 0.0430 mol) and nitromethane (3 ml) is cooled in an ice/water bath. Titanium tetrachloride (1M in dichloromethane, 88 ml, 0.088 mol) is added dropwise and the mixture is heated at 45 for 3 hr. After cooling, the mixture is poured onto ice/aqueous hydrochloric acid (1N) and extracted with dichloromethane. The combined organic layers are backwashed with hydrochloric acid (1N) and filtered through a pad of Celite topped with sodium sulfate. The filtrate is concentrated and chromatographed twice on silica gel eluding with ethyl acetate/hexane (5/95). The appropriate fractions are pooled and concentrated to give 6-chloro-1-(2-chloroethyl)isochroman (LXIV), NMR (CDCl3) 2.23, 2.70, 2.93, 3.75, 4.09, 4.89, 7.01 and 7.16 delta.

Reference： [1]Patent: US5877317,1999,A

37
[(3-Chloro-1-ethoxypropoxy)ethyl]benzene [ No CAS ]
[ 35573-93-4 ]
[ 2173-69-5 ]
[ 170856-60-7 ]

Yield	Reaction Conditions	Operation in experiment
	With hydrogenchloride; methanesulfonic acid;aluminium trichloride; In nitromethane;	Step 2 1-(2-Chloroethyl)-4,4-dimethylisochroman (LXIV) Methanesulfonic acid (0.21 g, 1.99 mmol) is added to a mixture of 3-chloropropionaldehyde diethyl acetal (LXII) and <strong>[2173-69-5]2-methyl-2-phenylpropanol</strong> (XLV, Step I, 2.93 g, 19.9 mmol) in nitromethane (15 ml) cooled to 0. After the addition the ice bath is removed and the reaction mixture is stirred overnight and then partitioned between ether and saline. The organic phase is separated and dried over magnesium sulfate, concentrated, and the residue chromatographed on silica gel eluding with a gradient of ethyl acetate/hexane (0.5/99.5 to 1/99 to 2/98). The appropriate fractions are pooled and concentrated to give the mixed acetal (LXIII). The mixed acetal (3.07 g, 11.3 mmol) is stirred at 0 in nitromethane (30 ml). Aluminum chloride (1.66 g, 12.4 mmol) is added over 10 min. The mixture is stirred an additional 25 min and then hydrochloric acid (4N, 4 ml) is added. The mixture is stirred for several minutes and then partitioned between dichloromethane, water, and aqueous sodium bicarbonate. The organic phase is separated, dried over sodium sulfate, concentrated and the residue chromatographed on silica gel (500 ml) eluding with an ethyl acetate/hexane gradient (0.5/99.5 to 2.5/97.5). The appropriate fractions are pooled and concentrated to give 1-(2-chloroethyl)-4,4-dimethylisochroman (LXIV), NMR (CDCl3) 1.23, 1.30, 2.31, 3.52, 3.66, 3.64, 3.81, 4.96, 7.05, 7.14-7.25 and 7.34 delta.

Reference： [1]Patent: US5877317,1999,A

38
[ 35573-93-4 ]
[ 60-12-8 ]
[(3-Chloro-1-ethoxypropoxy)ethyl]benzene [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
	With methanesulfonic acid In nitromethane	1 [(3-Chloro-1-ethoxypropoxy)ethyl]benzene (LXIII) PREPARATION 1 [(3-Chloro-1-ethoxypropoxy)ethyl]benzene (LXIII) 3-Chloropropionaldehyde diethyl acetal (LXII, 30.66 g, 0.184 mol) is added to an ice-cooled solution of phenethyl alcohol (XLV, 20.44 g, 0.167 mol) in nitromethane (50 ml) is added and methanesulfonic acid (1.61 g, 0.0167 mol). After 30 min the ice bath is removed and the mixture is allowed to stir overnight. The mixture is then warmed in a water bath at approximately 40°-50° under reduced pressure for 10-20 min (no appreciable removal of nitromethane occurs but there is some further reaction observed). The mixture is partitioned between ethyl ether and saline, the layers are separated and the organic phase is dried over magnesium sulfate and concentrated under reduced pressure. The crude material is stored overnight in the refrigerator and then chromatographed on silica gel eluding with hexane and then ethyl acetate/hexane (2/98). The appropriate fractions are pooled and concentrated to give the title compound, NMR (CDCl3) 1.20, 2.05, 2.87, 3.43-3.86, 4.69 and 7.24 δ.

Reference： [1]Current Patent Assignee: ZOETIS INC. - US5877317, 1999, A

39
methylene dichloride ether [ No CAS ]
[ 35573-93-4 ]
[ 1074-82-4 ]
[ 2453-90-9 ]

Yield	Reaction Conditions	Operation in experiment
60%	In 1-methyl-pyrrolidin-2-one	1 I. 1. Preparation of N-(3,3-diethoxypropyl)phthalimide (Compound 1), A mixture of 3-chloropropionaldehyde diethyl acetal (16.7 g, 0.10 mol) and potassium phthalimide (18.5 g, 0.10 mol) in N-methylpyrrolidinone (200 ml) was stirred overnight at 125° C. under nitrogen. The resulting solution was cooled and poured into water (400 ml) and the resulting mixture was extracted with ether (2200 ml). The ether extracts were washed with water (2100 ml), dried (MgSO4), filtered, and evaporated to leave an orange oil. Chromatography on silica (200 g) with 95:5 methylene chloride-ether provided pure Compound 1 as a pale orange oil (16.5 g, 60%).

Reference： [1]Current Patent Assignee: JOHNSON & JOHNSON INC - US5171754, 1992, A

40
3-(2,3-dihydro-1,5-diazaphenalen-1-yl)piperidine [ No CAS ]
[ 35573-93-4 ]
C₂₃H₃₃N₃O₂ [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
	With sodium hydroxide In ethanol; water at 0 - 50℃; for 12.5h;	1-19 Example 1-19; 1-[3-(Methylamino)propyl]-3-(2,3-dihydro-1,5-diazaphenalen-1-yl)piperidine; A mixed solvent of 3 N aqueous sodium hydroxide (8 ml) and ethanol (15 ml) was added with hydrochloride of 3-(2,3-dihydro-1,5-diazaphenalen-1-yl)piperidine obtained in Example 1-1, Step D (653 mg) under cooling on an ice bath, then added with 4-chlorobutylaldehyde diethyl acetal (1.08 g, Alfa Aesar), stirred at the same temperature for 30 minutes, and then further stirred at 50° C. for 12 hours. The reaction mixture was left to cool to room temperature, and then added with chloroform (30 ml) and saturated brine (20 ml), and the organic layer was separated. The aqueous layer was extracted 3 times with chloroform (20 ml for each time), and the combined organic layer was successively washed with water (30 ml), and saturated brine (30 ml) in this order, and dried over anhydrous magnesium sulfate. The organic layer was filtered through Celite, and then the solvent was evaporated under reduced pressure. The residue was purified by silica gel column chromatography (chloroform:methanol=20:1), added with 5 N hydrochloric acid (20 ml), and stirred at room temperature for 72 hours. The reaction mixture was cooled to 0° C., neutralized with 2 N aqueous sodium hydroxide (pH 7.5), and extracted 3 times with ethyl acetate (30 ml for each time). The combined organic layer was dried over anhydrous magnesium sulfate, and the solvent was evaporated under reduced pressure. The residue was dissolved in methanol (5 ml) and methylene chloride (10 ml), added with a 40% methylamine/methanol solution (8 ml, Tokyo Kasei Kogyo), and stirred at room temperature for 1 hour. Then, the reaction mixture was added with sodium borohydride (45 mg), and stirred at room temperature 16 hours. The reaction mixture was cooled to 0° C., added with water (20 ml), and extracted twice with methylene chloride (60 ml for each time). The combined organic layer was dried over anhydrous magnesium sulfate, and the solvent was evaporated under reduced pressure. The residue was purified by silica gel column chromatography (chloroform:methanol:isopropylamine=92.0/7.9/0.1) to obtain the title compound (203 mg). MS (m/z): 325 (MH+)

Reference： [1]Current Patent Assignee: ASAHI KASEI CORPORATION - US2006/247266, 2006, A1 Location in patent: Page/Page column 78

41
[ 35573-93-4 ]
3,3-diethoxypropyl benzoate [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
	With sodium benzoate In <i>N</i>-methyl-acetamide; diethyl ether	18.A Synthesis of 3-ethoxy-4-oxahexyl benzoate as an intermediate Step A Synthesis of 3-ethoxy-4-oxahexyl benzoate as an intermediate To a stirred solution of 5.0 grams (0.034 mole) of sodium benzoate in 100 ml of dimethylformamide was added 5.2 grams (0.031 mole) of 3-chloro-1,1-diethoxypropane. Upon completion of addition, the reaction mixture was warmed to reflux where it stirred for four hours. After this time the reaction mixture was cooled to ambient temperature and was filtered to remove a solid. The filtrate was diluted with water, and the mixture was extracted with diethyl ether. The combined extracts were dried with magnesium sulfate and filtered. The filtrate was concentrated under reduced pressure to a residual oil. The nmr spectrum indicated the presence of solvents. The oil was redissolved in diethyl ether and washed with water. The organic layer was dried with magnesium sulfate and filtered. The filtrate was concentrated under reduced pressure to a residual oil. The oil was evacuated under high vacuum yielding 6.3 grams of 3-ethoxy-4-oxahexyl benzoate. The nmr spectrum was consistent with the proposed structure.

Reference： [1]Current Patent Assignee: FMC CORP - US5081287, 1992, A

42
[ 35573-93-4 ]
[ 73942-87-7 ]
[ 102226-55-1 ]

Yield	Reaction Conditions	Operation in experiment
		(a) 3-(7,8-Dimethoxy-1,3-dihydro-2H-3-benzazepin-2-on-3-yl)-propionaldehyde diethyl acetal This is prepared analogously to Example H (a) by reacting <strong>[73942-87-7]7,8-dimethoxy-1,3-dihydro-2H-3-benzazepin-2-one</strong> with 3-chloro-propionaldehyde diethyl acetal.
		(a) 3-(7,8-Dimethoxy-1,3-dihydro-2H-3-benzazepin-2-on-3-yl)-propionaldehyde diethylacetal This compound is prepared analogously to Example I(a) by reacting <strong>[73942-87-7]7,8-dimethoxy-1,3-dihydro-2H-3-benzazepin-2-one</strong> with 3-chloro-propionaldehyde diethylacetal.

Reference： [1]Patent: US4584293,1986,A
[2]Patent: US4737495,1988,A

43
[ 35573-93-4 ]
[ 67-66-3 ]
[ 25519-78-2 ]
[ 108-10-1 ]
[1-(3,3-diethoxypropyl)-4-piperidinyl] (4-fluorophenyl)methanone [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
9 parts (53%)	With sodium carbonate; In methanol; water;	EXAMPLE VI A mixture of 4.5 parts of 1-chloro-3,3-diethoxypropane, 12.15 parts of (4-fluorophenyl) (4-piperidinyl)methanone hydrochloride, 10.6 parts of sodium carbonate and 120 parts of 4-methyl-2-pentanone is stirred and refluxed overnight. The reaction mixture is cooled, water is added and the layers are separated. The organic phase is dried, filtered and evaporated. The residue is purified by column-chromatography over silica gel using a mixture of trichloromethane and methanol (95:5 by volume) as eluent. The pure factors are collected and the eluent is evaporated. The residue is crystallized from a mixture of methylbenzene and 2,2'-oxybispropane, yielding 9 parts (53%) of [1-(3,3-diethoxypropyl)-4-piperidinyl] (4-fluorophenyl)methanone.

Reference： [1]Patent: US4335127,1982,A

44
[ 17198-23-1 ]
[ 35573-93-4 ]
[ 63590-83-0 ]

Yield	Reaction Conditions	Operation in experiment
	With potassium iodide In ethanol; water	2.A Preparation of 5-ethoxy-2,3,5,6-tetrahydro-6H-imidazo[2,1-b][1,3]thiazine Step A Preparation of 5-ethoxy-2,3,5,6-tetrahydro-6H-imidazo[2,1-b][1,3]thiazine A mixture of 35.7 g. of 2-thioimidazolidine, 87.5 g. of β-chloropropionaldehyde diethyl acetal and 11.62 g. of potassium iodide was refluxed in 1400 ml. of absolute ethanol for 4 days. The mixture was concentrated to dryness. The residue was dissolved in water, extracted with 6 portions of ether, basified with excess sodium hydroxide solution, and filtered. The filter cake was washed with water and chloroform. The filtrate and washings were extracted 8 times with chloroform. The extract was extracted with excess aqueous oxalic acid solution. This extract was basified and extracted with chloroform to give 31.3 g. (48%) of oily 5-ethoxy-2,3,5,6-tetrahydro-6H-imidazo[2,1-b][1,3]thiazine.

Reference： [1]Current Patent Assignee: MERCK & CO INC - US4025625, 1977, A

45
[ 35573-93-4 ]
[ 7417-21-2 ]
[ 62978-68-1 ]

Yield	Reaction Conditions	Operation in experiment
	With hydrogenchloride In water; acetone; benzene	6 EXAMPLE 6 EXAMPLE 6 To a mixture of 20 g of 3,4-dimethoxyphenethyl alcohol and 22 g of β-chloropropionaldehyde diethyl acetal was added 30 ml of concentrated hydrochloric acid, followed by heating at 60°-80° C with stirring for 25 minutes. After cooling, the reaction mixture was diluted with 100 ml of water and extracted with ethyl acetate. The extract was rinsed with water, dried and concentrated under reduced pressure. The resultant oil was chromatographed on a column of silica gel, followed by elution with a 1:9 mixture of acetone and benzene. By this procedure was obtained 6.9 g of 1-(2-chloroethyl)-6,7-dimethoxyisochroman as a colorless oil.

Reference： [1]Current Patent Assignee: TAKEDA PHARMACEUTICAL COMPANY LIMITED - US4066648, 1978, A

46
[ 35573-93-4 ]
2-amino-4,5-dihydro-4-ethoxy-6H-1,3-thiazine [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
	With potassium iodide; thiourea In ethanol	4.A Step A: Step A: Preparation of 2-amino-4,5-dihydro-4-ethoxy-6H-1,3-thiazine A mixture of 10 g. of thiourea, 50 ml. of β-chloropropionaldehyde diethyl acetal, 75 ml. of absolute ethanol, and 2 g. of potassium iodide was refluxed for 2 days. The solvent was evaporated, and the residue was partitioned between water and ether. The aqueous phase was extracted twice more with ether, basified with sodium carbonate and extracted 4 times with chloroform. The chloroform was concentrated to dryness, and the residue was thoroughly extracted with ether. The ether extracts were evaporated to a small volume which deposited 6.88 g. of crystalline 2-amino-4,5-dihydro-4-ethoxy-6H-1,3-thiazine.

Reference： [1]Current Patent Assignee: MERCK & CO INC - US4054652, 1977, A

47
[ 35573-93-4 ]
[ 13335-51-8 ]
1-(2-chloroethyl)-5,6-dimethoxyisochroman [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
	With hydrogenchloride In water	7 EXAMPLE 7 EXAMPLE 7 To a mixture of 20 g of 2,3-dimethoxyphenethyl alcohol and 22 g of β-chloropropionaldehyde diethyl acetal was added 30 ml of concentrated hydrochloric acid, followed by heating at 60°-85° C with stirring for 25 minutes. After cooling, the reaction mixture was diluted with 100 ml of water and extracted with ethyl acetate. The extract was rinsed with water, dehydrated, treated with activated carbon and concentrated under reduced pressure. By the above procedure was obtained 24 g of 1-(2-chloroethyl)-5,6-dimethoxyisochroman as a colorless oil.

Reference： [1]Current Patent Assignee: TAKEDA PHARMACEUTICAL COMPANY LIMITED - US4066648, 1978, A

48
[ 35573-93-4 ]
[ 5558-29-2 ]
[ 103545-98-8 ]

Yield	Reaction Conditions	Operation in experiment
	With oxalic acid; potassium carbonate In tetrahydrofuran; water; acetone; mineral oil	1.b b) b) 4-Cyano-5-methyl-4-phenylhexanal To a suspension of washed sodium hydride (50% in mineral oil) (14.4g, 0.30mol) in dry THF (200mL) was added 3-methyl-2-phenylbutanenitrile (40.0g, 0.25mol) in THF (100mL) over 10 minutes. The reaction mixture was heated to 60°C and maintained at that temperature until hydrogen evolution ceased. The reaction mixture was cooled to room temperature and 3-chloropropionaldehyde diethyl acetal (50g, 0.30mol) added dropwise. The reaction was heated at 60°C until complete by GC, then cooled, poured into ice/water and extracted into diethyl ether. The combined organic extracts were washed with brine, dried (MgSO4), filtered and evaporated in vacuoto a brown oil. The crude acetal was dissolved in acetone (200mL), and oxalic acid (24.9g, 0.28mol) in water (250mL) added. The reaction mixture was heated at reflux for 60 minutes, cooled to room temperature and neutralised by addition of solid potassium carbonate. Solids were filtered off and the filtrate concentrated in vacuo.The product was extracted from water into diethyl ether and washed with brine. The combined organic extracts were dried (MgSO4), filtered and evaporated. The resultant oil was purified by vacuum distillation (B.Pt. 102°C at 0.6mBar).

Reference： [1]Current Patent Assignee: ELI LILLY & CO - EP805147, 1997, A1

49
[ 198997-04-5 ]
[ 35573-93-4 ]
4-cyano-4-(1-methylethylsulfonyl)-4-phenylbutanal [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
	With sodium iodide; sodium; oxalic acid In ethanol; water; acetone	4.b b) b) 4-Cyano-4-(1-methylethylsulfonyl)-4-phenylbutanal To a solution of sodium (0.46g, 20mmol) in anhydrous ethanol (40mL) under nitrogen was added a solution of (1-methylethylsulfonyl)phenylacetonitrile (2.23g, 10mmol) in ethanol (5mL), After stirring at room temperature for 0.5h, a solution of 3-chloropropionaldehyde diethyl acetal (3.33g, 20mmol) in ethanol (5mL) was added, followed by anhydrous sodium iodide (3.0g, 20mmol). The solution was heated at reflux for 168h. The brown mixture was allowed to cool, poured into saturated aqueous ammonium chloride and extracted with ethyl acetate (3x). The combined organic extracts were washed with water (2x) and concentrated to an oil. This was taken up in acetone (30mL). A solution of oxalic acid (3.15g, 35mmol) in water (30mL) was added and the resulting solution heated at reflux for 1h. After cooling, the acetone was removed in vacuoand the aqueous residue extracted with ethyl acetate (3x). The combined organic extracts were washed with water, dried (MgSO4), filtered and concentrated. The residue was purified by flash chromatography on silica, eluding with ethyl acetate/hexane, to yield the aldehyde as a pale yellow oil.

Reference： [1]Current Patent Assignee: ELI LILLY & CO - EP805147, 1997, A1

50
[ 35573-93-4 ]
[ 90-14-2 ]
[ 960137-71-7 ]

Yield	Reaction Conditions	Operation in experiment
46%	With norborn-2-ene; caesium carbonate In acetonitrile at 90℃; for 24h;

Reference： [1]Mariampillai, Brian; Alliot, Julien; Li, Mengzhou; Lautens, Mark [Journal of the American Chemical Society, 2007, vol. 129, # 49, p. 15372 - 15379]

51
dihydroxyPEG [ No CAS ]
[ 35573-93-4 ]
[ 76-83-5 ]
Monotrityl PEG-monoacetal [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
	Stage #1: dihydroxyPEG; 3-chloro-1,1-diethoxy-propane With potassium <i>tert</i>-butylate In toluene Stage #2: trityl chloride In pyridine	6 Synthesis of a PharmaPEG-Monoaldehyde from PEG Diol Example 6 Synthesis of a PharmaPEG-Monoaldehyde from PEG Diol [0178] The synthesis of the monopropionaldehyde derivative of PharmaPEG is summarized in the following diagram, in which KOtBu denotes potassium t-butoxide, and DEP denotes the 3,3-diethoxypropyl group. [CHEMMOL-00003] [0179] Preferably, the dihydroxyPEG that is used as starting material for Step 1 will have a molecular weight that is within 10% of its nominal molecular weight and will have a polydispersity of <1.05. Polydispersity is defined as the ratio of the weight-average molecular weight (“Mw”) to the number-average molecular weight (“Mn”). Both of these parameters, Mw and Mn, can be measured by size-exclusion chromatography, using PEGs of accurately known molecular weights as standards and gel permeation chromatography software such as EZChrom Elite Client/Server Software, Version 2.8.3 (Scientific Software, Inc., Pleasanton, Calif.). Alternatively, the polydispersity of PEGs can be measured by matrix-assisted laser desorption/ionization time-of-flight (“MALDI-TOF”) mass spectroscopy (Marie, A., et al., (2000) Anal Chem 72:5106-5114), using software such as Voyager Software (Applied Biosystems, Foster City, Calif.). For the preparation of pharmaceutical products containing covalently linked PEG, the PEG starting material will preferably have a polydispersity of <1.02, and more preferably <1.01, when measured by MALDI-TOF mass spectroscopy. The starting material may be obtained from Aldrich Chemical Co., Fluka Chemicals (Buchs, Switzerland), Shearwater Corporation or from Sigma Chemical Co., among other suppliers that are known to those skilled in the art. If the starting material is not sufficiently homogeneous, it can be fractionated by an adaptation of the method described in Example 5. [0180] A mixture of monopropionaldehyde and dipropionaldehyde diethyl acetal derivatives of PEG diol can be synthesized using 3-chloro-propionaldehyde diethyl acetal (Aldrich catalog No.C6,900-4), as described for acetaldehyde diethyl acetal by Harris, J. M., et al., ((1984) J Polym Sci 22:341-352) (see Step 1). Similar methods were also described by Bentley, M. D., et al., ((1998) J Pharm Sci 87:1446-1449) and were subsequently patented by Bentley, M. D., et al. (U.S. Pat. No. 5,990,237). [0181] A sufficient quantity of triphenylmethyl chloride (chlorotriphenyl-methane or trityl chloride, Ph3CCl, e.g., Aldrich catalog No. T8,380-1) dissolved in pyridine is added to the mixture produced in Step 1 so that, under the reaction conditions, the Ph3CCl will react with all of the hydroxyl groups of the PEG starting material that are not coupled to the propionaldehyde diethyl acetal (Kocienski, P. J., supra). To complete Step 2, the mixture is recovered after precipitation by the addition of a poor solvent for PEG (e.g., ether) or by evaporation of the solvent or by other methods that are known in the art. [0182] The mixture recovered from Step 2 is dissolved in water before or after the addition of 5% (v/v) acetonitrile and the solution is loaded onto a reversed-phase column that is expected from principles known in the art to be capable of binding trityl derivatives of PEG. The column may contain alkyl or aryl derivatives of silica or a polymeric substrate, or it may be a styrene-based polymer (e.g., Amberchrom MD-P CG-300), as in Example 5. The PEG diol and trityl derivatives can be eluted in a reversed-phase mode with an increasing gradient of organic solvent, as in Example 5, or in a sample displacement mode by continuing to load the column until at least a portion of the desired species has been eluted (Agner, E., et al., PCT publication WO 00/23798 A1) (or in displacement mode (Cramer, S. M., U.S. Pat. No. 6,239,262), or in a combination of these modes. In general, the PEG derivative lacking any trityl group will elute first, the monotrityl derivative will elute second and the ditrityl PEG will elute third. An optimal yield of the desired product is obtained when the ratios of these three species are 1:2:1. To improve the yield and/or purity of the desired monotrityl PEG product, it may be desirable to subject a portion of the column effluent to recycling chromatography, as is well known in the chromatographic art. To complete Step 3, the portion of the eluate that contains at least a portion of the monotrityl derivative is separated, concentrated and dried by methods that are known in the art. [0183] Under mildly acidic conditions and at low temperature, the acetal can be converted to the aldehyde, while preserving most of the trityl linkage at the distal end of the PEG. In some applications of this example, it may be advantageous to react the monotrityl PEG monoaldehyde with a target moiety before removing the trityl group. Such embodiments are envisioned by and included in the present invention

Reference： [1]Current Patent Assignee: MOUNTAIN VIEW PHARMACEUTICALS INC - US2004/62746, 2004, A1 Location in patent: Page/Page column 21-22

52
[ 35573-93-4 ]
[ 78-94-4 ]
[ 1823-91-2 ]
7-methyl-7-phenyloctahydro-2H-quinolizin-2-one [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
	Stage #1: 1-phenylethyl cyanide With sodium hydride In N,N-dimethyl-formamide at 70℃; for 1h; Stage #2: 3-chloro-1,1-diethoxy-propane In N,N-dimethyl-formamide at 20 - 70℃; for 1h; Stage #3: methyl vinyl ketone With sodium hydroxide; lithium aluminium tetrahydride; sulfuric acid; water more than 3 stages;	1 EXAMPLE 1: EXAMPLE 1: Preparation of 1 and 2 following the procedure of Frank D. King, J Chem. Soc. Perkin Trans. 1, 447-453 (1986). To a suspension of dry DMF (100 ml) and sodium hydride, 60% (4.1 g, 0.17 mol) at 70 °C in a dry and inert atmosphere (Argon) methylphenylacetonitrile (10 ml, 0.075 mol) was added. After stirring at 70 °C for 1 h. 3-chloropropionaldehyde diethyl acetal (13.2 g, 0.079 mol) was added drop wise. After stirring at 70 °C for 1 h and cooling to RT, the reaction mixture was poured into I L of ice-water. The product was extracted with Et2O (3 x 200 ml). The combined Et2O extracts were filtered over Na2SO4 and evaporated in vac. to dryness yielding about 19.1 g of crude product which was directly used in the next step. To a suspension of dry THF (115 ml) and LAH (2.43 g, 0.065 mol) in a dry and inert atmosphere (Argon) concentrated sulphuric acid (1.6 ml, 0.03 mol) was added drop wise under cooling with ice water. After stirring at 0 °C for 1 h, a solution of the crude product from the previous step (19.1 g, 0.073 mol) in dry THF (19 ml) was added drop wise and the reaction mixture stirred at RT for 5 h. After cooling to 0 °C 1 M NaOH (11.3 ml) was added, the formed precipitate was removed by suction filtration and Et2O was used to wash the precipitate. The filtrate was evaporated in vac. to dryness yielding about 16 g crude product, which was dissolved in 65 ml Et2O. Methylvinylketone (6.1 ml, 0.073 mol) was added and the reaction mixture was stirred at RT for 2 h. The reaction mixture was added drop wise to 350 ml of 2.5 M HCl. The phases were separated with a separator funnel, the aqueous phase was taken and refluxed for 2h. After addition of ice cubes, the mixture was neutralized with solid sodium carbonate and extracted with CH2Cl2. The combined organic layers were dried over Na2SO4 and the solvent was removed in vac. to dryness. The crude product (11.2 g) was purified by CC method B. yielding 1 (2.9 g) and 2 (5.1 g). HPLC/MS Method A: 1: RTT = 2.7 [ms: 262.1 (M+H3O+), 244.1 (35%, M+H+)]; 2: RTT = 3.6 [ms: 262.1 (M+H3O+), 244.1 (25%, M+H+)]

Reference： [1]Current Patent Assignee: 55PHARMA DRUG DISCOVERY DEV - EP2072515, 2009, A1 Location in patent: Page/Page column 7

53
[ 35573-93-4 ]
[ 302557-44-4 ]
[ 1181975-81-4 ]

Yield	Reaction Conditions	Operation in experiment
	With tetra-(n-butyl)ammonium iodide In N,N-dimethyl-formamide at 50℃; for 24h;
	Stage #1: methyl 2,3,4,9-tetrahydro-1H-carbazole-6-carboxylate With sodium hydride In N,N-dimethyl-formamide at 20℃; for 0.25h; Stage #2: 3-chloro-1,1-diethoxy-propane With tetra-(n-butyl)ammonium iodide In N,N-dimethyl-formamide at 50℃; for 24h;	78.a To a stirred solution of 6,7,8,9-tetrahydro-5H-carbazole-3-carboxylic acid methyl ester (0.916 g, 4 mmol), in 12 ml of dry DMF, NaH (60% suspension in oil, 0.192 g, 4.8 mmol) was added portion wise. After stirring the reaction mixture for 15 min at r.t., 3- chloropropionaldehyde diethylacetal (1.01 ml, 6 mmol), in 4 ml of dry DMF, was added followed by the addition of TBAI (2.21 g, 6 mmol) and the reaction mixture was heated to 50 0C for 24 hrs. The DMF was removed in vacuo, the residue taken into EtOAc (100 ml), washed with H2O (40 ml) and sat.brine solution (40 ml). The organic layer was separated, dried over anhyd.MgSO4, solvents removed in vacuo and the crude product was purified by column chromatography, using EtOAc/hexane as eluents, to obtain 0.75 g of the product.

Reference： [1]Location in patent: scheme or table Mittapalli, Gopi Kumar; Jackson, Andrew; Zhao, Fang; Lee, Haekyung; Chow, Stephine; McKelvy, Jeffrey; Wong-Staal, Flossie; MacDonald, James E. [Bioorganic and Medicinal Chemistry Letters, 2011, vol. 21, # 22, p. 6852 - 6855]
[2]Current Patent Assignee: ITHERX PHARMACEUTICALS, INC. - WO2009/103022, 2009, A1 Location in patent: Page/Page column 86

54
[ 773837-37-9 ]
[ 35573-93-4 ]
[ 18381-45-8 ]

Yield	Reaction Conditions	Operation in experiment
94%	With tetra-(n-butyl)ammonium iodide In dimethyl sulfoxide at 50℃; for 15h;
86%	In dimethyl sulfoxide at 80℃; for 24h;

Reference： [1]Wang, Lihong; Prabhudas, Bodhuri; Clive, Derrick L. J. [Journal of the American Chemical Society, 2009, vol. 131, p. 6003 - 6012]
[2]Clausen, Florian; Studer, Armido [Organic Letters, 2020, vol. 22, # 17, p. 6780 - 6783]

55
[ 35573-93-4 ]
[ 107-12-0 ]
[ 1228894-06-1 ]

Yield	Reaction Conditions	Operation in experiment
53%	Stage #1: propiononitrile With lithium diisopropyl amide In tetrahydrofuran at -78℃; for 0.666667h; Stage #2: 3-chloro-1,1-diethoxy-propane In tetrahydrofuran at -78 - 20℃;

Reference： [1]Pitta, Bhaskar Reddy; Fleming, Fraser F. [Organic Letters, 2010, vol. 12, # 12, p. 2810 - 2813]

56
[ 119-61-9 ]
[ 35573-93-4 ]
[ 1233235-17-0 ]

Yield	Reaction Conditions	Operation in experiment
67%	Stage #1: 3-chloro-1,1-diethoxy-propane With magnesium; ethylene dibromide In tetrahydrofuran; toluene at 15 - 25℃; Stage #2: benzophenone In tetrahydrofuran; toluene at -30 - 0℃;

Reference： [1]Coric, Ilija; Vellalath, Sreekumar; List, Benjamin [Journal of the American Chemical Society, 2010, vol. 132, # 25, p. 8536 - 8537]

57
[ 98-03-3 ]
[ 35573-93-4 ]
[ 1258208-43-3 ]