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Product Details of [ 939-52-6 ]

CAS No. :939-52-6 MDL No. :MFCD00001005
Formula : C10H11ClO Boiling Point : -
Linear Structure Formula :- InChI Key :GHEFQKHLHFXSBR-UHFFFAOYSA-N
M.W : 182.65 Pubchem ID :253533
Synonyms :

Calculated chemistry of [ 939-52-6 ]

Physicochemical Properties

Num. heavy atoms : 12
Num. arom. heavy atoms : 6
Fraction Csp3 : 0.3
Num. rotatable bonds : 4
Num. H-bond acceptors : 1.0
Num. H-bond donors : 0.0
Molar Refractivity : 51.05
TPSA : 17.07 Ų

Pharmacokinetics

GI absorption : High
BBB permeant : Yes
P-gp substrate : No
CYP1A2 inhibitor : Yes
CYP2C19 inhibitor : No
CYP2C9 inhibitor : No
CYP2D6 inhibitor : Yes
CYP3A4 inhibitor : No
Log Kp (skin permeation) : -5.41 cm/s

Lipophilicity

Log Po/w (iLOGP) : 2.12
Log Po/w (XLOGP3) : 2.82
Log Po/w (WLOGP) : 2.89
Log Po/w (MLOGP) : 2.69
Log Po/w (SILICOS-IT) : 3.35
Consensus Log Po/w : 2.77

Druglikeness

Lipinski : 0.0
Ghose : None
Veber : 0.0
Egan : 0.0
Muegge : 2.0
Bioavailability Score : 0.55

Water Solubility

Log S (ESOL) : -2.86
Solubility : 0.255 mg/ml ; 0.0014 mol/l
Class : Soluble
Log S (Ali) : -2.84
Solubility : 0.266 mg/ml ; 0.00146 mol/l
Class : Soluble
Log S (SILICOS-IT) : -4.18
Solubility : 0.0122 mg/ml ; 0.0000667 mol/l
Class : Moderately soluble

Medicinal Chemistry

PAINS : 0.0 alert
Brenk : 1.0 alert
Leadlikeness : 1.0
Synthetic accessibility : 1.22

Safety of [ 939-52-6 ]

Signal Word:Warning Class:N/A
Precautionary Statements:P261-P305+P351+P338 UN#:N/A
Hazard Statements:H315-H319-H335 Packing Group:N/A
GHS Pictogram:

Application In Synthesis of [ 939-52-6 ]

* All experimental methods are cited from the reference, please refer to the original source for details. We do not guarantee the accuracy of the content in the reference.

  • Downstream synthetic route of [ 939-52-6 ]

[ 939-52-6 ] Synthesis Path-Downstream   1~78

  • 1
  • [ 57988-60-0 ]
  • [ 939-52-6 ]
  • [ 59995-69-6 ]
YieldReaction ConditionsOperation in experiment
With toluene; potassium iodide
  • 3
  • [ 4635-59-0 ]
  • [ 71-43-2 ]
  • [ 939-52-6 ]
YieldReaction ConditionsOperation in experiment
92% With aluminum (III) chloride at 5℃; for 1.5h;
92% With aluminum (III) chloride at 5℃; for 1.5h;
85.9% With aluminium trichloride at 0 - 20℃; for 2h;
78.4% With aluminium trichloride at 20℃; for 1h;
71% In carbon disulfide for 2h; Ambient temperature;
70%
With aluminium trichloride
With carbon disulfide; aluminium trichloride for 1h; Heating;
With aluminium trichloride for 0.5h; Ambient temperature;
With aluminum (III) chloride In dichloromethane at 0 - 25℃; for 3h; Inert atmosphere; Generalprocedure for the synthesis of γ-chlorobutyrophenone (7a-e) General procedure: 4-Chlorobutyryl chloride (2.5 mL, 21.25 mmol, 1.0 equiv), benzene (10 mL, 106.25 mmol, 5.0 equiv) and dry dichloromethane (30 mL) was taken in a round bottom flask under nitrogen atmosphere. The solution was cooled to 0 C and aluminum chloride(3.3 g) was added portion wise at ice cooled condition. The resulting suspension was stirred for 3 h at 25 C. The reaction was quenched by pouring the orange colored solution into an ice/water mixture. Dichloromethane was used to extract the desired product, and the organic layer was washed with brine (10 mL), dried withNa2SO4, and concentrated in vacuo. The desired product (7a) was purified via column chromatography using eluent pet ether-ethyl acetate (98:2). Similar procedure was followed for the synthesis of substituted c-chlorobutyrophenones (7b-e).
With aluminum (III) chloride at 0 - 20℃; for 2.08333h; General procedure: Anhydrous aluminum trichloride (3 g, 22 mmol) was added in portions under stirring to a solution of ω-chlorocarboxylic acid chloride (20 mmol) and aromatic hydrocarbon (25 mmol) in a solvent (an excess of the same aromatic hydrocarbon or methylene chloride, 10 mL) cooled to 0 °C for 5 min, and the resulting solution was stirred for 1 h at 0 °C and then 1 h at 20 °C. The mixture was poured onto ice (20 g), the organic layer was separated, and the aqueous layer was extracted with methylene chloride (3 × 30 mL). The extracts were united, dried with anhydrous sodium sulfate, and the solvent was evaporated. The residue was purified by column chromatography (l = 5 cm, d = 5 cm) on silica gel eluting with methylene chloride. The chromatographically homogeneous product was used without further purification for the synthesis of alkylating agents (IIa)-(IIm) as described below.
With aluminum (III) chloride In dichloromethane
With aluminum (III) chloride In dichloromethane at 0 - 20℃; Inert atmosphere;
With aluminum (III) chloride In dichloromethane at 0 - 20℃; Inert atmosphere;

Reference: [1]Location in patent: experimental part Husar, Branislav; Lukac, Ivan; Chmela, Stefan; Canet, Jean-Louis; Troin, Yves [Chemical Papers, 2010, vol. 64, # 4, p. 499 - 503]
[2]Husár, Branislav; LukáĿ, Ivan; Chmela, ſtefan; Canet, Jean-Louis; Troin, Yves [Chemical Papers, 2010, vol. 64, # 4, p. 499 - 503]
[3]Kritzyn; Komissarov [Russian Journal of Bioorganic Chemistry, 2005, vol. 31, # 6, p. 549 - 555]
[4]Schliemann; Buege; Reppel [Pharmazie, 1980, vol. 35, # 3, p. 140 - 143]
[5]Khalaf, Ali A.; Abdel-Wahab, Aboel-Magd A.; El-Khawaga, Ahmed M.; El-Zohry, Maher F. [Bulletin de la Societe Chimique de France, 1984, vol. 2, # 7-8, p. 285 - 291]
[6]Wagner, Peter J.; Frerking, Harlan W. Jr. [Canadian Journal of Chemistry, 1995, vol. 73, p. 2047 - 2061]
[7]Janssen et al. [Journal of medicinal and pharmaceutical chemistry, 1959, vol. 1, p. 281,284]
[8]Bordwell,F.G.; Brannen,W.T. [Journal of the American Chemical Society, 1964, vol. 86, p. 4645 - 4650]
[9]Wagner, Peter J.; Lindstrom, Michael J. [Journal of the American Chemical Society, 1987, vol. 109, # 10, p. 3057 - 3062]
[10]Matveeva; Kvasha; Kurts [Russian Journal of Organic Chemistry, 1996, vol. 32, # 1, p. 21 - 24]
[11]Chowdhury, Nilanjana; Dutta, Sansa; Karthick; Anoop, Anakuthil; Dasgupta, Swagata; Pradeep Singh [Journal of Photochemistry and Photobiology B: Biology, 2012, vol. 115, p. 25 - 34]
[12]Komissarov; Valuev-Elliston; Ivanova; Kochetkov; Kritzyn [Russian Journal of Bioorganic Chemistry, 2015, vol. 41, # 1, p. 37 - 45][Bioorg. Khim., 2015, vol. 41, # 1, p. 44 - 53,10]
[13]Loman, Jacob. J.; Carnaghan, Emma R.; Hamlin, Trevor A.; Ovian, John M.; Kelly, Christopher B.; Mercadante, Michael A.; Leadbeater, Nicholas E. [Organic and Biomolecular Chemistry, 2016, vol. 14, # 16, p. 3883 - 3888]
[14]Huang, Fei; Zhang, Songlin [Organic Letters, 2019, vol. 21, # 18, p. 7430 - 7434]
[15]Wang, Yiqiong; Huang, Fei; Zhang, Songlin [European Journal of Organic Chemistry, 2020, vol. 2020, # 32, p. 5178 - 5181]
  • 4
  • [ 939-52-6 ]
  • [ 3481-02-5 ]
YieldReaction ConditionsOperation in experiment
91% With sodium hydroxide In 1,4-dioxane; water
84% With α-naphthol; sodium hydroxide In tetrahydrofuran; water at 20℃; for 20h; Green chemistry; General Experimental Procedure General procedure: A solution of 2-Naphthol (865mg, 6 mmol) in THF (3 ml) was added dropwise to the solution of sodium hydroxide (0.3g, 7.5mmol) in H2O(1.5 ml) at room tempera-ture. The mixture was stirred for 15 min. Thensolution of 3-chloro-1-phenylacetone (843.1 mg, 5 mmol) in THF (3 ml) was added slowly. Afteraddition, the mixture was stirred for another 2 h. TLC indicated the3-chloro-1-phenyl acetone was consumed up. Thenethyl acetate and water were added, after separation, the organic phasewas washed with brine, dried over Na2SO4 ,thenconcentrated. The residue was purified via flash column chromatography on silica gel
79% With potassium hydroxide In methanol cooling to 20 deg C;
78% With sodium hydroxide In water Heating;
With potassium hydroxide
With methanol; potassium cyanide
With potassium hydroxide In ethanol for 0.5h; Yield given;

  • 5
  • [ 107-21-1 ]
  • [ 939-52-6 ]
  • [ 3308-98-3 ]
YieldReaction ConditionsOperation in experiment
99% With toluene-4-sulfonic acid In benzene at 90℃; for 18h;
85% With toluene-4-sulfonic acid; orthoformic acid triethyl ester Ambient temperature;
84% With toluene-4-sulfonic acid; orthoformic acid triethyl ester In toluene for 8h; Heating;
77% With toluene-4-sulfonic acid In toluene Dean-Stark; Reflux;
68%
64% With toluene-4-sulfonic acid In benzene Heating;
With toluene-4-sulfonic acid In benzene for 5h; Heating;
With toluene-4-sulfonic acid In benzene Heating;
In benzene for 96h; Heating; Yield given;
With toluene-4-sulfonic acid Heating;
In toluene Reflux; Dean-Stark trap; 8 Another beta-carboline derivative was prepared using the procedures outlined in Scheme 4. Ketone 26 as converted to ketal 27 and then this material was used to N- alkylate harmine to give 28. Removal of the ketal gave ketone 29, which was reduced with sodium borohydride to yield 30. The alcohol was converted to the imide 31, which was treated with hydrazine hydrate to give amine 32. Scheme 4. (a) (HOCH2)2, TsOH, toluene, reflux, Dean-Stark trap; (b) harmine, NaH, DMF, rt; (c) Aq. HCl, MeOH, rt; (d) NaBH4, THF, rt; (e) phthalimide, DEAD, Ph3P, THF, rt; (f) ΝΗ2ΝΗ2·Η20, MeOH, DCM.

Reference: [1]Zhang, Han-Cheng; Harris, Bruce D.; Costanzo, Michael J.; Lawson, Edward C.; Maryanoff, Cynthia A.; Maryanoff, Bruce E. [Journal of Organic Chemistry, 1998, vol. 63, # 22, p. 7964 - 7981]
[2]Vieira, Eric; Binggeli, Alfred; Breu, Volker; Bur, Daniel; Fischli, Walter; Gueller, Rolf; Hirth, Georges; Maerki, Hans Peter; Mueller, Marcel; Oefner, Christian; Scalone, Michelangelo; Stadler, Heinz; Wilhelm, Maurice; Wostl, Wolfgang [Bioorganic and Medicinal Chemistry Letters, 1999, vol. 9, # 10, p. 1397 - 1402]
[3]Kritzyn; Komissarov [Russian Journal of Bioorganic Chemistry, 2005, vol. 31, # 6, p. 549 - 555]
[4]Willand-Charnley, Rachel; Puffer, Benjamin W.; Dussault, Patrick H. [Journal of the American Chemical Society, 2014, vol. 136, # 16, p. 5821 - 5823]
[5]Current Patent Assignee: BRISTOL-MYERS SQUIBB CO - US6348472, 2002, B1 Location in patent: Page column 10
[6]Karachev; Popkov [Chemistry of Heterocyclic Compounds, 2005, vol. 41, # 8, p. 987 - 993]
[7]Wills, Max T.; Wills, Irene E.; Dollen, Lawrence Von; Butler, Barry L.; Porter, John; Anderson, Arthur G. [Journal of Organic Chemistry, 1980, vol. 45, # 12, p. 2489 - 2498]
[8]Hoefle, M. L.; Blouin, L. T.; Fleming, R. W.; Hastings, S.; Hinkley, J. M.; et al. [Journal of Medicinal Chemistry, 1991, vol. 34, # 1, p. 12 - 19]
[9]Purchase II, Claude F.; Goel, O. P. [Journal of Organic Chemistry, 1991, vol. 56, # 1, p. 457 - 459]
[10]Hulshof, Janneke W.; Casarosa, Paola; Menge, Wiro M. P. B.; Kuusisto, Leena M. S.; Van Der Goot, Henk; Smit, Martine J.; De Esch, Iwan J. P.; Leurs, Rob [Journal of Medicinal Chemistry, 2005, vol. 48, # 20, p. 6461 - 6471]
[11]Current Patent Assignee: MASS GENERAL BRIGHAM INC - WO2011/133795, 2011, A2 Location in patent: Page/Page column 28-29
  • 6
  • [ 137-07-5 ]
  • [ 939-52-6 ]
  • [ 87696-87-5 ]
YieldReaction ConditionsOperation in experiment
73% With pyridine In toluene Heating;
  • 7
  • [ 1501-05-9 ]
  • [ 939-52-6 ]
YieldReaction ConditionsOperation in experiment
60% With tert-butylhypochlorite; silver triflate-bis(1,10-phenanthroline) complex In acetonitrile at 45℃; for 23h; Inert atmosphere;
With lead(IV) acetate; lithium chloride 1) benzene, 25 deg C, 1 h, 2) reflux, 2 h; Yield given. Multistep reaction;
  • 8
  • [ 15336-98-8 ]
  • [ 939-52-6 ]
  • [ 87372-61-0 ]
YieldReaction ConditionsOperation in experiment
61% With tetraethylammonium chloride In 1,2-dichloro-ethane at 80℃; for 22h;
  • 9
  • [ 939-52-6 ]
  • [ 6072-57-7 ]
YieldReaction ConditionsOperation in experiment
70% In neat (no solvent) at 90℃; for 1h;
  • 10
  • [ 939-52-6 ]
  • [ 65488-05-3 ]
YieldReaction ConditionsOperation in experiment
88% With sodium iodide In acetone for 10h; Heating;
81% With sodium iodide In acetone for 10h; Reflux; Inert atmosphere; Schlenk technique; regioselective reaction;
80% With sodium iodide In acetone for 18h; Inert atmosphere; Reflux;
80% With sodium iodide In acetone for 8h; Reflux;
78% With sodium iodide In butanone for 2h; Heating;
59% With sodium iodide In acetone for 16h; Reflux; 81 Preparation of 4-iodo-l -phenylbutan-l -one; [0298] Sodium iodide (1.64 g, 10.95 mmol, 2 equiv) was added to a solution of 4-chloro-l- phenylbutan-l-one (1 g, 5.475 mmol, 1 equiv) in acetone. The reaction mixture was refluxed for 16 h. After cooling to ambient temperature, it was evaporated under reduced pressure to remove all the acetone. The residue was worked up using ethyl acetate and sodium bisulfite, followed by a wash with brine. The organic layer was dried over MgSO i, filtered and concentrated in vacuo. The crude residue was purified using the Biotage falsh chromatography system (SNAP 50g cartridge, R/= 0.4, 5 %-30% ethyl acetate in hexanes) to afford the title compound as white solid (880 mg, 59%). The bottle containing the compound was wrapped in aluminium foil to stored in the freezer to avoid further darkening of the mixture; 'HNMR (400 MHz, DMSO-i/6): δ 2.06-2.16 (m, 2H); 3.14 (t, 2H, J= 3.2 and 4 Hz); 3.34 (t, 2H, J= 6.8 and 7.2 Hz); 7.51-7.55 (m, 2H); 7.62-7.67 (m, 2H); 7.95-7.98 (m, 2H); MS for C10HuIO m/z 274.99 (M+H)+.
With sodium iodide In butanone
With sodium iodide In acetone for 6h; Heating;
3 g With sodium iodide In acetone for 6h; Heating;
With sodium iodide In acetone for 1.5h; Heating / reflux; 54 497 mg (2.720 mmol) of 4-chlorobutyrophenone and 445 mg (2.968 mmol) of sodium iodide were refluxed in 30 ml acetone for 1.5 hours to obtain the iodo derivative. The reaction was monitored by TLC and also visually by the precipitation of sodium chloride. To this slurry was added 500 mg (2.473 mmol) of 5-hydroxypsoralen, an excess (2 g) of anhydrous potassium carbonate and it was refluxed for 140 hours. The progress of the reaction was monitored by thin layer chromatography. After 140 hours the reaction mixture was concentrated under reduced pressure. The oily residue was cooled and diluted with water. The aqueous solution was then acidified with concentrated hydrochloric acid to pH 1. The slurry was stirred for 15-20 min, filtered and washed with water and dried under vacuum. The solids were suspended in 50 ml ethyl acetate and refluxed to separate the un-reacted 5-hydroxypsoralen. The ethyl acetate layer was concentrated, the resulting residue dissolved in 100 ml dichloromethane and extracted with 25 ml of 1% sodium hydroxide to separate the remaining trace amounts of un-reacted 5-hydroxypsoralen. The dichloromethane layer was washed with 30 ml of 2% hydrochloric acid solution, dried over anhydrous sodium sulfate and concentrated. The solid residue obtained was dissolved in a methanol-acetone mixture, treated with charcoal and re-crystallized from a petroleum ether-acetone (90:10) mixture. Yield: 295.2 mg (34.27%) Melting point: 129.1° C. 1H-NMR (500 MHz, CDCl3): δ [ppm]=8.13 (d, 1H, 3J=9.9 Hz, 3-H), 8.01 (d, 2H, 3J=7.9 Hz, 4J=0.95 Hz, 2-H, 6-H), 7.62 (t, 1H, 3J=7.4 Hz, 3-H, 5-H), 7.60 (d, 1H, 3J=2.4 Hz, 2'-H), 7.50 (t, 2H, 3J=7.7 Hz, 4-H), 7.15 (s, 1H, 8-H), 6.99 (d, 1H, 3J=2.5 Hz, 3'-H), 6.26 (d, 1H, 3J=9.8 Hz, 4-H) 4.59 (t, 2H, 3J=6.2 Hz, 5-OCH2CH2CH2COC6H5), 3.28 (t, 2H, 3J=6.8 Hz, 5-OCH2CH2CH2COC6H5), 2.38 (p, 2H, 3J=6.5 Hz, 5-OCH2CH2CH2COC6H5). MS (70 eV) m/z: 348 (34%, M+), 202 (5%, M+-C10H10O), 147(99%, C10H10O), 174, (5%, [202-CO]+), 105 (71%, C3H6), 77 (33%, C6H5). Combustion analysis: (FW: 348.36) % C 71.68, % H 5.25 (Calc. % C 72.41, % H 4.63)

Reference: [1]Zhou, Jianrong; Fu, Gregory C. [Journal of the American Chemical Society, 2003, vol. 125, # 48, p. 14726 - 14727]
[2]Huang, Feng-Qing; Xie, Jian; Sun, Jian-Guo; Wang, Yue-Wei; Dong, Xin; Qi, Lian-Wen; Zhang, Bo [Organic Letters, 2016, vol. 18, # 4, p. 684 - 687]
[3]Location in patent: experimental part Park, Ju-Young; Kim, Seung-Woo; Lee, Ja-Kyeong; Im, Weon Bin; Jin, Byung Kwan; Yoon, Sung-Hwa [Biological and Pharmaceutical Bulletin, 2011, vol. 34, # 4, p. 538 - 544]
[4]Li, Wei; Tan, Fei; Hao, Xiaoyu; Wang, Gang; Tang, Yu; Liu, Xiaohua; Lin, Lili; Feng, Xiaoming [Angewandte Chemie - International Edition, 2015, vol. 54, # 5, p. 1608 - 1611][Angew. Chem., 2014, vol. 127, # 5, p. 1628 - 1631,4]
[5]Wagner, Peter J.; Frerking, Harlan W. Jr. [Canadian Journal of Chemistry, 1995, vol. 73, p. 2047 - 2061]
[6]Current Patent Assignee: TAKEDA PHARMACEUTICAL COMPANY LIMITED - WO2011/160084, 2011, A1 Location in patent: Page/Page column 104
[7]Yamaguchi,S.; Kabuto,K. [Bulletin of the Chemical Society of Japan, 1977, vol. 50, # 11, p. 3033 - 3038]
[8]Zhang; Ter Laak; Timmerman [European Journal of Medicinal Chemistry, 1993, vol. 28, # 2, p. 165 - 173]
[9]Khorana, Nantaka; Bondarev, Mikhail; Dukat, Malgorzata; Herrick-Davis, Katharine; Egan, Christina; DuPre, Ann; Smith, Carol; Teitler, Milt; Glennon, Richard A. [Medicinal Chemistry Research, 1999, vol. 9, # 9, p. 657 - 667]
[10]Current Patent Assignee: UNIVERSITY OF CALIFORNIA - US2006/79535, 2006, A1 Location in patent: Page/Page column 31
  • 11
  • [ 939-52-6 ]
  • [ 33553-82-1 ]
YieldReaction ConditionsOperation in experiment
96% With sodium tetrahydroborate In methanol at 0℃; for 0.5h; Inert atmosphere; Schlenk technique; regioselective reaction;
90% With sodium tetrahydroborate In methanol at 0℃;
78% With sodium tetrahydroborate In tetrahydrofuran at 0℃; for 1h;
70% With tri-n-butyl-tin hydride; silica gel In dichloromethane for 24h; Ambient temperature;
65% With sodium tetrahydroborate In ethanol at 0 - 20℃; for 2h; 4-Chloro-1-phenyl-1-butanol (13) To a solution of 4-chlorobutyrophenone (5.11 g, 28.0 mmol) in ethanol (50 mL) wasadded NaBH4 (0.821 g, 21.7 mmol) at 0 °C and the mixture was warmed to roomtemperature with stirring for 2 h. HClaq (1 M, 100 mL) was added at 0 °C. The mixture was extracted with ethyl acetate (2 x 100 mL) and washed with water (2 x 150 mL). Thecombined organic layer was dried over MgSO4 and evaporated. The residue waspurified by column chromatography (EtOAc) to give the product (3.37 g, 65%). Thespectral data were exactly matched to the reported data.40
61% With (2-((dimethylamino)methyl)phenyl)dimethyltin; phenylsilane In methanol at 20℃;
With sodium tetrahydroborate; sodium hydrogencarbonate In ethanol for 1h; Ambient temperature;
With sodium tetrahydroborate; sodium hydrogencarbonate In ethanol for 1h; Ambient temperature;
With bis(1,5-cyclooctadiene)rhodium(I) tetrafluoroborate; (S,S)-2,2"-bis<(diethylphosphino)methyl>-1,1"-biferrocene; potassium carbonate; bis(3-fluorophenyl)silane 1.) -40 deg C, THF, 24 h; 2.) 4 h, r.t., MeOH; Yield given; Multistep reaction;
With sodium tetrahydroborate In ethanol at 0 - 20℃;
With sodium tetrahydroborate; sodium hydrogencarbonate In ethanol
With hydrogenchloride; sodium tetrahydroborate In tetrahydrofuran 22.a a a α-(3-Chloropropyl)benzenemethanol A mixture of 4-chloro-1-phenyl-1-butanone (7.35 g) and sodium tetrahydroborate (3.05 g) in tetrahydrofuran (40 ml) was stirred for 36 h. 2M Hydrochloric acid was added and the mixture was extracted three times with ethyl acetate. The combined organic extracts were dried (magnesium sulphate), evaporated and purified by chromatography on silica eluding with petrol-ether to give the sub-title compound as a colourless oil (6.60 g). 1H NMR 300 MHz (CDCl3) 7.41-7.23 (5H, m), 4.70 (1H, t), 3.62-3.49 (2H, m), 1.98-1.76 (5H, m).
With sodium tetrahydroborate In methanol
With lithium aluminium tetrahydride In diethyl ether at 0℃; for 2h;
With sodium tetrahydroborate; ethanol at 0 - 20℃; Inert atmosphere; Schlenk technique;
With methanol; sodium tetrahydroborate at 0 - 20℃; Inert atmosphere; Sealed tube;

Reference: [1]Huang, Feng-Qing; Xie, Jian; Sun, Jian-Guo; Wang, Yue-Wei; Dong, Xin; Qi, Lian-Wen; Zhang, Bo [Organic Letters, 2016, vol. 18, # 4, p. 684 - 687]
[2]Mansueto, Rosmara; Mallardo, Valentina; Perna, Filippo Maria; Salomone, Antonio; Capriati, Vito [Chemical Communications, 2013, vol. 49, # 86, p. 10160 - 10162]
[3]Zhang, Han-Cheng; Harris, Bruce D.; Costanzo, Michael J.; Lawson, Edward C.; Maryanoff, Cynthia A.; Maryanoff, Bruce E. [Journal of Organic Chemistry, 1998, vol. 63, # 22, p. 7964 - 7981]
[4]Figadere; Chaboche; Franck; Peyrat; Cave [Journal of Organic Chemistry, 1994, vol. 59, # 23, p. 7138 - 7141]
[5]Nishimoto, Yoshihiro; Yazawa, Satoshi; Kiyokawa, Kensuke; Kajiki, Takahito; Tsukahara, Yasunori; Yamauchi, Tomohisa; Wada, Yuji; Baba, Akio; Yasuda, Makoto [Chemistry Letters, 2017, vol. 46, # 8, p. 1116 - 1118]
[6]Vedejs, E.; Duncan, S. M.; Haight, A. R. [Journal of Organic Chemistry, 1993, vol. 58, # 11, p. 3046 - 3050]
[7]Almena, Juan; Foubelo, Francisco; Yus, Miguel [Tetrahedron, 1996, vol. 52, # 25, p. 8545 - 8564]
[8]Almena, Juan; Foubelo, Francisco; Yus, Miguel [Tetrahedron, 1997, vol. 53, # 15, p. 5563 - 5572]
[9]Kuwano; Uemura; Saitoh; Ito [Tetrahedron Letters, 1999, vol. 40, # 7, p. 1327 - 1330]
[10]Hulshof, Janneke W.; Casarosa, Paola; Menge, Wiro M. P. B.; Kuusisto, Leena M. S.; Van Der Goot, Henk; Smit, Martine J.; De Esch, Iwan J. P.; Leurs, Rob [Journal of Medicinal Chemistry, 2005, vol. 48, # 20, p. 6461 - 6471]
[11]Hulshof, Janneke W.; Vischer, Henry F.; Verheij, Mark H.P.; Fratantoni, Silvina A.; Smit, Martine J.; de Esch, Iwan J.P.; Leurs, Rob [Bioorganic and Medicinal Chemistry, 2006, vol. 14, # 21, p. 7213 - 7230]
[12]Current Patent Assignee: ASTRAZENECA PLC - US2003/105161, 2003, A1
[13]Loman, Jacob. J.; Carnaghan, Emma R.; Hamlin, Trevor A.; Ovian, John M.; Kelly, Christopher B.; Mercadante, Michael A.; Leadbeater, Nicholas E. [Organic and Biomolecular Chemistry, 2016, vol. 14, # 16, p. 3883 - 3888]
[14]Bafaluy, Daniel; Muñoz-Molina, José María; Funes-Ardoiz, Ignacio; Herold, Sebastian; de Aguirre, Adiran J.; Zhang, Hongwei; Maseras, Feliu; Belderrain, Tomás R.; Pérez, Pedro J.; Muñiz, Kilian [Angewandte Chemie - International Edition, 2019, vol. 58, # 26, p. 8912 - 8916][Angew. Chem., 2019, vol. 131, # 36, p. 9004 - 9009,6]
[15]Chang, Xiao-Yong; Chen, Ji-Jun; Gu, Qiang-Shuai; Jiang, Sheng-Peng; Li, Zhong-Liang; Liu, Lin; Liu, Xiao-Dong; Liu, Xin-Yuan; Su, Xiao-Long; Wang, Fu-Li; Yang, Chang-Jiang; Ye, Liu [Angewandte Chemie - International Edition, 2021, vol. 60, # 1, p. 380 - 384][Angew. Chem., 2021, vol. 133, # 1, p. 384 - 388,5]
[16]Liu, Zhi-Yun; Cook, Silas P. [Organic Letters, 2021, vol. 23, # 3, p. 808 - 813]
  • 13
  • [ 939-52-6 ]
  • C10H11O(1+)*F6Sb(1-) [ No CAS ]
YieldReaction ConditionsOperation in experiment
55% With silver hexafluoroantimonate In trifluoroacetic acid at 20℃; for 1.5h;
  • 14
  • [ 1779-49-3 ]
  • [ 939-52-6 ]
  • [ 16675-51-7 ]
YieldReaction ConditionsOperation in experiment
17% Stage #1: Methyltriphenylphosphonium bromide With potassium <i>tert</i>-butylate In tetrahydrofuran at 0℃; for 0.5h; Stage #2: 4-chloro-1-phenylbutan-1-one In tetrahydrofuran for 12h;
(i) nBuLi, (ii) /BRN= 878974/; Multistep reaction;
Stage #1: Methyltriphenylphosphonium bromide With potassium <i>tert</i>-butylate In tetrahydrofuran at 0℃; for 0.75h; Stage #2: 4-chloro-1-phenylbutan-1-one In tetrahydrofuran at 0 - 20℃;
  • 15
  • [ 939-52-6 ]
  • [ 69573-41-7 ]
YieldReaction ConditionsOperation in experiment
99% With sodium azide In dimethyl sulfoxide at 55℃; for 60h; 71.A Step A: Preparation of 4-azido-l-phenylbutan-l-one: To a solution of 4- chloro-1-phenylbutan-l-one (26.4 mL, 164 mmol) in DMSO (200 mL) was added sodium azide (12.8 g, 197 mmol). The solution was warmed to 55 °C and stirred for 16 hours. The cooled mixture was then treated with water (600 mL) and extracted with ether (3 x 200 mL). The combined organics were washed with water (8 x 100 mL) and brine (100 mL) then dried over MgSO4 and concentrated to provide the product as an orange oil (30.7 g, 99%).
99% With sodium azide In dimethyl sulfoxide at 55℃; for 16h; 5.A Example 5l-(3-((Λ')-5-(2.5-diϖuorophcnyl)-3-((.S')-2-niethθxypropanoylV2-phenyl-2,3-dilivdro-l .3.4-tliiadiayχ>l-2-yl)propyl)-2-methoxyauanidine hydrochloride(001941 Step A: Preparation of 4-azido-l-phenylbutan-l-one: To a solution of 4-chloro-l- phenylbutan-1-one (26.4 mL, 164 mmol) in DMSO (200 ml) was added sodium azide (12.8 g, 197 mmol). The solution was warmed to 55°C and stirred for 16 hours. The cooled mixture was then treated with water and extracted with ether. The combined organics were washed with water and brine, then dried over MgS04 and concentrated to provide the product as an orange oil (30.7 g,
95% With sodium azide In water; dimethyl sulfoxide for 0.133333h; microwave irradiation;
95% With sodium azide In N,N-dimethyl-formamide
94% With sodium azide In N,N-dimethyl-formamide at 70℃; for 2h; Inert atmosphere; Schlenk technique; regioselective reaction;
85% With sodium azide In N,N-dimethyl-formamide at 50℃; for 2h; General procedure for the synthesis of γ-azidobutyrophenone (8a-e) General procedure: General procedure for the synthesis of γ-azidobutyrophenone (8a-e) The 4-chlorobutyrophenone 7a (2.5 g, 12.6 mmol) was dissolved in DMF (20 mL) and solid NaN3 (2.1 g, 25.2 mmol) was added and heated up to 50 °C and stirred for 2 h. After completion of the reaction, the reaction mixture was diluted with EtOAc and washed with water. The organic layer was separated and dried with Na2SO4.The solvent was evaporated and purified by column chromatography using pet ether-ethyl acetate (95:5) yielded γ-azidobutyrophenone (8a). The above mentioned procedure was carried out for the synthesis of other γ-azidobutyrophenones (8b-e).
With sodium azide; sodium iodide In dimethyl sulfoxide at 55℃; for 12h; Yield given;
With sodium azide; tetrabutyl-ammonium chloride In 1,2-dimethoxyethane at 75℃; for 16h;
With sodium azide In dimethyl sulfoxide at 55℃;
With sodium azide In N,N-dimethyl-formamide at 75℃;
With sodium azide In N,N-dimethyl-formamide at 90℃;
With sodium azide In N,N-dimethyl-formamide at 60℃;

Reference: [1]Current Patent Assignee: PFIZER INC - WO2006/44825, 2006, A2 Location in patent: Page/Page column 95
[2]Current Patent Assignee: PFIZER INC - WO2008/42928, 2008, A2 Location in patent: Page/Page column 35-36
[3]Singh, Pradeep N. D.; Muthukrishnan, Sivaramakrishnan; Murthy, Rajesh S.; Klima, Rodney F.; Mandel, Sarah M.; Hawk, Michael; Yarbrough, Nina; Gudmundsdottir, Anna D. [Tetrahedron Letters, 2003, vol. 44, # 51, p. 9169 - 9172]
[4]Weinstein, David S.; Liu, Wen; Ngu, Khehyong; Langevine, Charles; Combs, Donald W.; Zhuang, Shaobin; Chen, Cindy; Madsen, Cort S.; Harper, Timothy W.; Robl, Jeffrey A. [Bioorganic and Medicinal Chemistry Letters, 2007, vol. 17, # 18, p. 5115 - 5120]
[5]Huang, Feng-Qing; Xie, Jian; Sun, Jian-Guo; Wang, Yue-Wei; Dong, Xin; Qi, Lian-Wen; Zhang, Bo [Organic Letters, 2016, vol. 18, # 4, p. 684 - 687]
[6]Chowdhury, Nilanjana; Dutta, Sansa; Karthick; Anoop, Anakuthil; Dasgupta, Swagata; Pradeep Singh [Journal of Photochemistry and Photobiology B: Biology, 2012, vol. 115, p. 25 - 34]
[7]De Kimpe, Norbert; Tehrani, Kourosch Abbaspour; Stevens, Christian; De Cooman, Paul [Tetrahedron, 1997, vol. 53, # 10, p. 3693 - 3706]
[8]Karoui, Hakim; Nsanzumuhire, Celine; Le Moigne, Francois; Tordo, Paul [Journal of Organic Chemistry, 1999, vol. 64, # 2-5, p. 1471 - 1477]
[9]Dickerson, Tobin J.; Janda, Kim D. [Journal of the American Chemical Society, 2002, vol. 124, # 13, p. 3220 - 3221]
[10]Nguyen, Kevin T.; Claiborne, Christopher F.; McCauley, John A.; Libby, Brian E.; Claremon, David A.; Bednar, Rodney A.; Mosser, Scott D.; Gaul, Stanley L.; Connolly, Thomas M.; Condra, Cindra L.; Bednar, Bohumil; Stump, Gary L.; Lynch, Joseph J.; Koblan, Kenneth S.; Liverton, Nigel J. [Bioorganic and Medicinal Chemistry Letters, 2007, vol. 17, # 14, p. 3997 - 4000]
[11]Location in patent: scheme or table Ngu, Khehyong; Weinstein, David S.; Liu, Wen; Langevine, Charles; Combs, Donald W.; Zhuang, Shaobin; Chen, Xing; Madsen, Cort S.; Harper, Timothy W.; Ahmad, Saleem; Robl, Jeffrey A. [Bioorganic and Medicinal Chemistry Letters, 2011, vol. 21, # 14, p. 4141 - 4145]
[12]Florentino, Lucía; López, Lucía; Barroso, Raquel; Cabal, María-Paz; Valdés, Carlos [Angewandte Chemie - International Edition, 2021, vol. 60, # 3, p. 1273 - 1280][Angew. Chem., 2021, vol. 133, # 3, p. 1293 - 1300,8]
  • 16
  • [ 58113-36-3 ]
  • [ 939-52-6 ]
  • 4-{4-[Bis-(4-fluoro-phenyl)-methylene]-piperidin-1-yl}-1-phenyl-butan-1-one [ No CAS ]
  • 17
  • [ 939-52-6 ]
  • [ 65488-06-4 ]
  • (R)-4-chloro-1-phenyl-1-butanol [ No CAS ]
YieldReaction ConditionsOperation in experiment
With dimethylsulfide borane complex; N-(di-p-anisylphosphoryl)-(S)-α,α-diphenyl-2-pyrrolidinemethanol In toluene at 110℃; Title compound not separated from byproducts;
Stage #1: 4-chloro-1-phenylbutan-1-one With (S,S)-2,2"-bis<(diethylphosphino)methyl>-1,1"-biferrocene; bis(3-fluorophenyl)silane In tetrahydrofuran at -40℃; for 24h; Stage #2: With methanol; potassium carbonate In tetrahydrofuran at 20℃; for 4h; Title compound not separated from byproducts;
87 % ee With sodium t-butanolate; <i>tert</i>-butyl alcohol; (S)-2,2',6,6'-tetramethoxy-4,4'-bis(di(3,5-xylyl)phosphino)-3,3'-bipyridine In toluene at 0℃; for 14h; Overall yield = 90 %;
  • 18
  • [ 195006-97-4 ]
  • [ 939-52-6 ]
  • (2R)-2-phenyl-2,3-propylen-(1-dodecyl 2-amino-4,6-O-benzylidene-2,3-dideoxy-β-D-allopyranoside)[2,3-d][1,3]oxazolidine [ No CAS ]
YieldReaction ConditionsOperation in experiment
62% With triethylamine In dichloromethane at 20℃;
  • 19
  • [ 13509-52-9 ]
  • [ 939-52-6 ]
  • 1,3-dimethyl-6-(2-phenyl-tetrahydro-furan-2-ylmethyl)-1<i>H</i>-pyrimidine-2,4-dione [ No CAS ]
  • 20
  • [ 94815-76-6 ]
  • [ 939-52-6 ]
  • 2-methoxy-3-methyl-6-(2-phenyl-tetrahydro-furan-2-ylmethyl)-3<i>H</i>-pyrimidin-4-one [ No CAS ]
YieldReaction ConditionsOperation in experiment
15% Stage #1: 6-methyl-3-methyl-2-methoxy-4-pyrimidinone With lithium diisopropyl amide In tetrahydrofuran at -78℃; for 0.5h; Stage #2: 4-chloro-1-phenylbutan-1-one In tetrahydrofuran at -78 - -70℃; for 6h; Further stages.;
  • 21
  • [ 213266-70-7 ]
  • [ 939-52-6 ]
  • 3-methyl-6-(2-phenyl-tetrahydro-furan-2-ylmethyl)-2-propoxy-3<i>H</i>-pyrimidin-4-one [ No CAS ]
YieldReaction ConditionsOperation in experiment
36% Stage #1: 2-n-propyloxy-3,6-dimethyl-4(3H)-pyrimidinone With lithium diisopropyl amide In tetrahydrofuran at -78℃; for 0.5h; Stage #2: 4-chloro-1-phenylbutan-1-one In tetrahydrofuran at -78 - -70℃; for 6h; Further stages.;
  • 22
  • [ 68965-63-9 ]
  • [ 939-52-6 ]
  • [ 439579-50-7 ]
YieldReaction ConditionsOperation in experiment
45% Stage #1: N,N-Dimethyl-2-brom-1-cyclohexencarboxamid With tert.-butyl lithium In tetrahydrofuran at -78℃; for 1h; Stage #2: 4-chloro-1-phenylbutan-1-one In tetrahydrofuran at -50℃; for 0.25h; Further stages.;
  • 23
  • [ 16502-01-5 ]
  • [ 939-52-6 ]
  • 1-phenyl-4-(1,3,4,9-tetrahydro-β-carbolin-2-yl)-butan-1-one [ No CAS ]
YieldReaction ConditionsOperation in experiment
11% With sodium carbonate; potassium iodide In N,N-dimethyl-formamide at 65℃; for 3.5h;
  • 24
  • [ 939-52-6 ]
  • [ 16133-83-8 ]
  • [ 65488-06-4 ]
  • (R)-4-chloro-1-phenyl-1-butanol [ No CAS ]
YieldReaction ConditionsOperation in experiment
With (-)-sparteine In methanol at 50℃; for 40h;
  • 25
  • 9-(3-chloro-propyl)-9-bora-bicyclo[3.3.1]nonane [ No CAS ]
  • [ 380451-93-4 ]
  • [ 939-52-6 ]
YieldReaction ConditionsOperation in experiment
21% With tetrakis(triphenylphosphine) palladium(0); copper(I) thiophene-2-carboxylate; caesium carbonate In tetrahydrofuran at 45℃; for 16h;
  • 26
  • [ 939-52-6 ]
  • [ 700-91-4 ]
YieldReaction ConditionsOperation in experiment
95% With sodium azide; triethyl phosphite In dimethyl sulfoxide for 0.333333h; microwave irradiation;
Multi-step reaction with 2 steps 1: NaN3 / dimethylsulfoxide / 55 °C 2: PPh3 / hexane
Multi-step reaction with 2 steps 1: NaN3, NaI / dimethylsulfoxide / 12 h / 55 °C 2: 95 percent / Ph3P / pentane / 14 h / Ambient temperature
Multi-step reaction with 4 steps 1: p-Toluenesulfonic acid / benzene / 5 h / Heating 2: dimethylformamide 3: 1.) KOH, 2.) HCl / 1.) ethanol/water, 6 h, reflux 4: p-Toluenesulfonic acid / benzene / Heating
Multi-step reaction with 2 steps 1: sulfuric acid / ethanol / 45 °C / Inert atmosphere 2: iodine; samarium / tetrahydrofuran / 1 h / 20 °C / Inert atmosphere; Schlenk technique
Multi-step reaction with 2 steps 1: sulfuric acid / ethanol / 45 °C / Inert atmosphere 2: ytterbium / tetrahydrofuran / 4 h / 60 °C / Inert atmosphere

  • 27
  • [ 486-60-2 ]
  • [ 939-52-6 ]
  • KP-1 [ No CAS ]
  • 28
  • [ 939-52-6 ]
  • 2-<i>tert</i>-butoxy-3,6-dimethyl-3<i>H</i>-pyrimidin-4-one [ No CAS ]
  • 2-butoxy-3-methyl-6-(2-phenyl-tetrahydro-furan-2-ylmethyl)-3<i>H</i>-pyrimidin-4-one [ No CAS ]
YieldReaction ConditionsOperation in experiment
63% Stage #1: 2-<i>tert</i>-butoxy-3,6-dimethyl-3<i>H</i>-pyrimidin-4-one With lithium diisopropyl amide In tetrahydrofuran at -78℃; for 0.5h; Stage #2: 4-chloro-1-phenylbutan-1-one In tetrahydrofuran at -78 - -70℃; for 6h; Further stages.;
  • 29
  • [ 628-20-6 ]
  • [ 98-80-6 ]
  • [ 939-52-6 ]
YieldReaction ConditionsOperation in experiment
35% In nitromethane for 24h; Heating;
13% With [2,2]bipyridinyl; potassium fluoride; acetic acid In tetrahydrofuran at 80℃; for 48h;
  • 30
  • [ 100-52-7 ]
  • [ 939-52-6 ]
  • 4-chloro-2-(hydroxy-phenyl-methyl)-1-phenyl-butan-1-one [ No CAS ]
YieldReaction ConditionsOperation in experiment
73% Stage #1: 4-chloro-1-phenylbutan-1-one With lithium diisopropyl amide In tetrahydrofuran; n-heptane; ethylbenzene at -75℃; for 0.0166667h; Stage #2: benzaldehyde In tetrahydrofuran; n-heptane; ethylbenzene at -75℃; for 0.05h;
  • 31
  • [ 100-52-7 ]
  • [ 939-52-6 ]
  • trans-3-benzoyl-2-phenyltetrahydrofuran [ No CAS ]
YieldReaction ConditionsOperation in experiment
44% With potassium <i>tert</i>-butylate In ethanol at -18 - 10℃; for 6h;
  • 32
  • [ 106-95-6 ]
  • [ 939-52-6 ]
  • (+)-1-chloro-4-phenylhept-6-en-4-ol [ No CAS ]
  • (-)-1-chloro-4-phenylhept-6-en-4-ol [ No CAS ]
YieldReaction ConditionsOperation in experiment
With chloro-trimethyl-silane; N-Boc-L-prolinamide derivative; triethylamine In tetrahydrofuran at 0℃; for 24h; Title compound not separated from byproducts;
  • 33
  • [ 387827-25-0 ]
  • [ 939-52-6 ]
  • N-{3-[1-(4-oxo-4-phenylbutyl)-4-piperidinyl]phenyl}acetamide [ No CAS ]
YieldReaction ConditionsOperation in experiment
71% With potassium carbonate; N-ethyl-N,N-diisopropylamine In 1,4-dioxane for 16h; Heating;
  • 34
  • [ 603-33-8 ]
  • [ 4635-59-0 ]
  • [ 939-52-6 ]
YieldReaction ConditionsOperation in experiment
89% With triethylamine In 1,4-dioxane at 80℃; for 3h;
  • 35
  • [ 939-52-6 ]
  • [ 1006-64-0 ]
YieldReaction ConditionsOperation in experiment
Multi-step reaction with 3 steps 1: NaN3 / dimethylsulfoxide / 55 °C 2: PPh3 / hexane 3: NaBH4; AcOH / methanol
Multi-step reaction with 5 steps 1: p-Toluenesulfonic acid / benzene / 5 h / Heating 2: dimethylformamide 3: 1.) KOH, 2.) HCl / 1.) ethanol/water, 6 h, reflux 4: p-Toluenesulfonic acid / benzene / Heating 5: LiAlH4 / diethyl ether / Ambient temperature
  • 36
  • [ 939-52-6 ]
  • [ 3308-99-4 ]
YieldReaction ConditionsOperation in experiment
Multi-step reaction with 2 steps 1: p-Toluenesulfonic acid / benzene / 5 h / Heating 2: dimethylformamide
  • 37
  • [ 939-52-6 ]
  • [ 5294-61-1 ]
  • N-(2,6-dimethylphenyl)-2-[4-(4-oxo-4-phenylbutyl)piperazin-1-yl]acetamide [ No CAS ]
YieldReaction ConditionsOperation in experiment
With triethylamine; In ethanol; for 16.0h;Heating / reflux; A mixture OF N- (2, 6-dimethylphenyl) -2-piperazinylacetamide (4) (100 mg, 0.4 mmol), 4- CHLORO-1-PHENYLBUTAN-1-ONE (12) (100 mg, 0.55 mmol), and triethylamine (0.4 mL) in ethanol (3 mL) was heated at reflux for 16 hours. Ethanol was removed under reduced pressure and the residue was purified by preparative TLC using 10% methanol in dichloromethane as mobile phase to afford N (2, 6-dimethylphenyl)-2- [4- (4-oxo-4-phenylbutyl) piperazin-1-yl] acetamide, a compound of formula (16).
  • 38
  • [ 118-92-3 ]
  • [ 939-52-6 ]
  • [ 122478-56-2 ]
YieldReaction ConditionsOperation in experiment
41.1 g (81.5%) With toluene-4-sulfonic acid In 5,5-dimethyl-1,3-cyclohexadiene 49.a a) a) 1,2,3,3a-Tetrahydro-3a-phenyl-5H-pyrrolo[1,2-a]-3,1-benzoxazin-5-one (Formula IV, R3 =H, X=C6 H5) A mixture of 26.1 g of 2-aminobenzoic acid, 36.5 g of 4-chloro-1-phenyl-1-butanone, 0.5 g of p-toluenesulfonic acid and 250 ml of xylene were refluxed with a water trap. After the reaction was complete, the solvent was removed by distillation and the remaining solid was recrystallized from ethanol. Yield: 41.1 g (81.5%), melting point 152° C.
  • 39
  • [ 122368-54-1 ]
  • 4-[(4-chlorophenyl)-pyridin-2-ylmethoxy]-1-(3-benzoylpropyl)piperidine [ No CAS ]
  • [ 939-52-6 ]
YieldReaction ConditionsOperation in experiment
EXAMPLE 49 From 4-[(4-chlorophenyl)-2-pyridylmethoxy]piperidine and 3-chloro-1-benzoylpropane, 4-[(4-chlorophenyl)-2-pyridylmethoxy]-1-(3-benzoylpropyl)piperidine was obtained in the same procedure as described in Example 26. Mass analysis value: EI-MS M+ no peak, CI-MS m/e=449(M+ +1). 1 H-NMR(CDCl3): delta(ppm)=1.88(2H,b), 2.11(4H,b,m), 2.67(4H,b), 2.94(2H,b), 3.10(2H,t), 3.63(1H,m), 5.57(1H,s), 7.14-7.72(10H,m), 7.96(2H,m), 8.51(1H,m).
  • 40
  • [ 589-57-1 ]
  • [ 4830-93-7 ]
  • [ 116652-96-1 ]
  • [ 939-52-6 ]
  • [ 85672-92-0 ]
YieldReaction ConditionsOperation in experiment
With hydrogen; iodine; magnesium In ethanol 2.a (a) (a) (4-Phenylbutyl)phosphonous acid, diethyl ester (4-Chloro-1-oxobutyl)benzene (164 ml., 1 mole), 5% palladium on carbon catalyst (25 g.) and 1 l. of absolute ethanol are shaken in a 2 l. Parr vessel under 40-50 psi of hydrogen for 24 hours. The mixture is filtered and the filtrate is concentrated in vacuo to yield 183 g. of crude product. The crude product is distilled to yield 155 g. of (4-chlorobutyl)benzene. 220 ml. of a solution of (4-chlorobutyl)benzene (1083 g., 6.42 mole) in 1280 ml. of ether is added to a flask containing magnesium (241.6 g., 0.9 mole) in 834 ml. of ether. The mixture is refluxed and a few crystals of iodine are added. The reaction initiates after about 30 minutes. When the initial reaction subsides, the remaining chloride solution is added at a rate sufficient to maintain reflux (addition time about 1.5 hours). Reflux is maintained an additional 2.5 hours and the mixture is cooled and allowed to stir overnight under argon at room temperature to give the Grignard solution, (4-phenylbutyl) magnesium chloride. Diethylchlorophosphite (914 g., 5.84 mole) and ether (5.12 l.) are combined and cooled to 5°-10°. The (4-phenylbutyl) magnesium chloride solution is added with stirring at a rate sufficient to maintain the reaction temperature below 15° (1.5 hours addition time). The cooling bath is removed and the mixture is stirred 30 minutes at room temperature. The mixture is filtered, the filtrate is concentrated under argon, and the residue is distilled to yield 1120 g. of (4-phenylbutyl) phosphonous acid, diethyl ester; b.p. 114°-119°/0.7 mm.
With hydrogen; iodine; magnesium In ethanol 3.a (a) (a) (4-Phenylbutyl)phosphonous acid, diethyl ester (4-Chloro-1-oxobutyl)benzene (164 ml., 1 mole), 5% palladium on carbon catalyst (25 g.) and 1 l. of absolute ethanol are shaken in a 2 l. Parr vessel under 40-50 psi of hydrogen for 24 hours. The mixture is filtered and the filtrate is concentrated in vacuo to yield 183 g. of crude product. The crude product is distilled to yield 155 g. of (4-chlorobutyl)benzene. 220 ml. of a solution of (4-chlorobutyl)benzene (1083 g., 6.42 mole) in 1280 ml. of ether is added to a flask containing magnesium (241.6 g., 0.9 mole) in 834 ml. of ether. The mixture is refluxed and a few crystals of iodine are added. The reaction initiates after about 30 minutes. When the initial reaction subsides, the remaining chloride solution is added at a rate sufficient to maintain reflux (addition time about 1.5 hours). Reflux is maintained an additional 2.5 hours and the mixture is cooled and allowed to stir overnight under argon at room temperature to give the Grignard solution, (4-phenylbutyl)magnesium chloride. Diethylchlorophosphite (914 g., 5.84 mole) and ether (5.12 l.) are combined and cooled to 5°-10°. The (4-phenylbutyl)magnesium chloride solution is added with stirring at a rate sufficient to maintain the reaction temperature below 15° (1.5 hours addition time). The cooling bath is removed and the mixture is stirred 30 minutes at room temperature. The mixture is filtered, the filtrate is concentrated under argon, and the residue is distilled to yield 1120 g. of (4-phenylbutyl)phosphonous acid, diethyl ester; b.p. 114°-119°/0.7 mm.
  • 41
  • [ 563-41-7 ]
  • [ 939-52-6 ]
  • semicarbazone [ No CAS ]
  • [ 75343-29-2 ]
YieldReaction ConditionsOperation in experiment
With sodium acetate In ethanol; water 2.i (i) (i) 4-Chloro-1-phenylbutan-1-one semicarbazone A mixture of semicarbazide hydrochloride (1.5 g. 10 mmol), anhydrous sodium acetate (1.65 g. 20 mmol), 4-chloro-1-phenylbutan-1-one (1,46 g, 8 mmol), water (10 ml), and ethanol (30 ml) was stirred at 20° for 2 h and then more water (30 ml) was added and the mixture left to crystallise for 16 h at 5°. Filtration then gave the semicarbazone as colourless rhombs which were dried and triturated with ether to give the pure semicarbazone as a white powder, (0.9 g, 47%). mp 132°-134°, νmax (KBr) 3470, 1680, 1575, 1460 cm-1; λmax (EtOH) 207 nm (εm 23,800), 276 nm (εm 26,700); δH (CDCl3)9.75 (1H, 5, NH), 7.3-7.5, 7.6-7.8 (5H, 2m, aryl), 5.95 (2H, bs, NH2), 3.70 (2H, t, H4), 2.90 (2H, m, H2), 2.00 (2H, m, H3).
  • 42
  • [ 593-56-6 ]
  • [ 939-52-6 ]
  • 1-chloro-4-phenylbutan-4-one O-methyloxime [ No CAS ]
YieldReaction ConditionsOperation in experiment
84% With pyridine In ethanol 5 4-Methoxyimino-4-phenylbutyl monate A EXAMPLE 5 4-Methoxyimino-4-phenylbutyl monate A A mixture of 1-chloro-4-phenylbutan-4-one (1.83 g, 10 mmol), O-methylhydroxylammonium chloride (1.67 g, 20 mmol), pyridine (1.21 ml, 15 mmol), and ethanol (15 ml) was heated at reflux for 1 hour and then evaporated in vacuo. The residue was partitioned between chloroform and water, and the organic layer was dried (MgSO4) and evaporated in vacuo to give 1-chloro-4-phenylbutan-4-one O-methyloxime (1.78 g, 84%), νmax (neat) 2930, 1445, 1050, 900 cm-1; λmax (EtOH) 209 nm (εm 17,200), 253 nm (εm 11,100); δH (CDCl3) 7.3-7.8 (5H, m, aryl), 3.9 (3H, s, OMe), 3.5 (2H, t, H1), 2.9 (2H, t, H3), 2.0 (2H, qn, H2).
  • 43
  • [ 126-30-7 ]
  • [ 939-52-6 ]
  • [ 56327-34-5 ]
YieldReaction ConditionsOperation in experiment
With toluene-4-sulfonic acid In benzene Ethyl 6,6-(2,2-dimethyltrimethylene-1,3-dioxy)-2-oxo-6-phenylhexanoate (Note 4) A solution of 3-chloropropyl phenyl ketone (23 g.), 2,2-dimethylpropane-1,3-diol (66 g.) and p-toluenesulphonic acid (0.5 g.) in benzene (300 ml.) was heated under reflux for 12 hours in a Dean and Stark water-separating apparatus, cooled and filtered. The filtrate was poured onto a silica gel column which was then eluted with toluene. The elude was evaporated to dryness and there was thus obtained 2-(3-chloropropyl)-5,5-dimethyl-2-phenyl-1,3-dioxan.
  • 44
  • methanolic hydrogen chloride [ No CAS ]
  • [ 56277-21-5 ]
  • [ 939-52-6 ]
  • 6-(3-benzoylpropyl)-6-azabicyclo[3.2.1]octane hydrochloride [ No CAS ]
  • 4-[1-(3-methoxy-phenyl)-6-aza-bicyclo[3.2.1]oct-6-yl]-1-phenyl-butan-1-one [ No CAS ]
YieldReaction ConditionsOperation in experiment
With potassium iodide; potassium carbonate In hexane; water; toluene; benzene 11 1-(3-methoxyphenyl)-6-(3-benzoylpropyl)-6-azabicyclo[3,2,1]octane EXAMPLE 11 1-(3-methoxyphenyl)-6-(3-benzoylpropyl)-6-azabicyclo[3,2,1]octane A mixture of 0.8 g of 1-(3-methoxyphenyl)-6-azabicyclo[3,2,1]octane, 0.74 g of 3-benzoylpropyl chloride, 0.8 g of potassium carbonate, 0.05 g of potassium iodide and 20 ml of toluene is refluxed for 24 hours. After cooling, water is added to the mixture, and the aqueous mixture is extracted with ether. The ether extract is washed with water, dried and then evaporated to remove solvent. The residue thus obtained is dissolved in 2 ml of benzene. The benzene solution is poured onto a column of 50 g of aluminium oxide. Then, the column is eluted with a mixture of 400 ml of benzene and 400 ml of n-hexane, and the effluent is evaporated to remove solvent. Methanolic hydrogen chloride is added to the residue in ether, and the crystalline precipitate is collected by filtration. The precipitate is recrystallized from a mixture of ethanol and ether. 0.485 g of 1-(3-methoxyphenyl)- 6-(3-benzoylpropyl)-6-azabicyclo[3,2,1]octane hydrochloride is obtained. M.p. 167° - 169°C.
  • 45
  • [ 23906-13-0 ]
  • [ 939-52-6 ]
  • 1-(4,6-dimethyl-2-pyrimidinyl)-1,4,5,6-tetrahydro-3-phenylpyridazine [ No CAS ]
YieldReaction ConditionsOperation in experiment
With sodium hydrogencarbonate; triethylamine; In ethyl acetate; isopropyl alcohol; EXAMPLE 2 Synthesis of 1-(4,6-dimethyl-2-pyrimidinyl)-1,4,5,6-tetrahydro-3-phenylpyridazine 4-Chloro-1-phenyl-1-butanone (2.00 g, 11.0 mmol), 4,6-dimethyl-2-hydrazinylpyrimidine (1.50 g, 10.9 mmol) and triethylamine (3 mL) are combined in 60 mL of 2-propanol. The solution is heated at reflux overnight. The solvent is removed and the residue is partitioned between 75 mL of 5% sodium bicarbonate solution and 75 mL of ethyl acetate. The organic portion is separated and the aqueous portion is extracted with ethyl acetate (75 mL). The two organic portions are combined, washed with 50 mL brine, dried (MgSO4) and the solvent is removed. The residue is purified by chromatography to give 0.58 g of 1-(4,6-dimethyl-2-pyrimidinyl)-1,4,5,6-tetrahydro-3-phenyl-pyridazine as a solid: mp 95-97C. 1H NMR (CDCl3) delta 2.11 (m, 2H), 2.42 (s, 6H), 2.71 (t, 2H), 4.10 (t, 2H), 6.50 (s, 1H), 7.30 (m, 3H), 7.90 (m, 2H).
  • 46
  • [ 75-77-4 ]
  • [ 939-52-6 ]
  • [ 1003601-43-1 ]
YieldReaction ConditionsOperation in experiment
81% With lithium chloride In tetrahydrofuran at 0℃; for 8h;
80% With 1,4-dioxane; lithium chloride; 2-mesitylmagnesium bromide In tetrahydrofuran at 0℃; for 1h; Inert atmosphere;
  • 47
  • [ 4651-72-3 ]
  • [ 939-52-6 ]
  • [ 960617-92-9 ]
YieldReaction ConditionsOperation in experiment
82% With chloro-trimethyl-silane In N,N-dimethyl-formamide at 100℃; for 14h;
  • 48
  • [ 939-52-6 ]
  • [ 149-73-5 ]
  • [ 409334-96-9 ]
YieldReaction ConditionsOperation in experiment
95% With Montmorillonite K10 clay for 72h; Inert atmosphere;
87% With toluene-4-sulfonic acid In methanol at 25℃; for 18h; Inert atmosphere;
  • 49
  • [ 939-52-6 ]
  • [ 343338-28-3 ]
  • [ 1218989-24-2 ]
YieldReaction ConditionsOperation in experiment
91% With titanium (IV) ethoxide In tetrahydrofuran at 65℃; for 48h; Inert atmosphere;
  • 50
  • [ 196929-78-9 ]
  • [ 939-52-6 ]
  • [ 1227798-49-3 ]
YieldReaction ConditionsOperation in experiment
86% With titanium(IV) tetraethanolate In neat (no solvent) at 72℃; Inert atmosphere;
With titanium(IV) tetraethanolate In tetrahydrofuran Reflux;
  • 51
  • [ 103-67-3 ]
  • [ 939-52-6 ]
  • [ 735240-08-1 ]
YieldReaction ConditionsOperation in experiment
80% Stage #1: 4-chloro-1-phenylbutan-1-one With sodium iodide In acetone Heating / reflux; Stage #2: benzyl-methyl-amine With potassium carbonate In acetone Heating / reflux; 1.a Example I (a): Synthesis of 4-(N-benzyl-N-methylamino)- 1 -phenylbutan- 1 -one (Precursor 1): A solution of 4-chloro-l -phenylbutan- 1 -one (10.0 g, 0.05 mole) in 75 ml of acetone that had been saturated with sodium iodide (NaI) was refluxed overnight. The acetone was removed at reduced pressure. Water (20 ml) was added, and the crude product was obtained by extracting with ether (2 x 20 ml). The combined ether layer was washed with fresh water and brine and dried over magnesium sulfate (MgSO4). After removing the ether on a rotary evaporator, a reddish oily crude product was obtained and used as such for the next step. The crude product obtained in the previous step was dissolved in 50 ml acetone, and 2.42 g (0.05 mole) of N- benzyl methylamine and 6.91 g (0.05 mole) of potassium carbonate (K2 CO3) was then added. The reaction mixture was refluxed overnight. After removing acetone at reduced pressure, water was added and the product was isolated in dichloromethane from the aqueous solution. The organic layer was washed with fresh water and brine, and dried over magnesium sulfate. The product (9.52 g, 80%) was obtained as reddish oil after removing dichloromethane on a rotary evaporator.
  • 52
  • [ 64214-66-0 ]
  • [ 100-58-3 ]
  • [ 939-52-6 ]
  • 53
  • [ 1314099-29-0 ]
  • [ 939-52-6 ]
  • [ 1314099-36-9 ]
YieldReaction ConditionsOperation in experiment
97% Stage #1: B-allenyl-1,3,2-dioxaborolane With (S)-3,3'-dibromo-1,1'-bi-2-naphthol at 20℃; for 0.0833333h; Inert atmosphere; Neat (no solvent); Stage #2: 4-chloro-1-phenylbutan-1-one at 71℃; for 0.75h; Inert atmosphere; Neat (no solvent); Microwave irradiation; optical yield given as %ee; enantioselective reaction;
  • 54
  • [ 939-52-6 ]
  • [ 52868-14-1 ]
YieldReaction ConditionsOperation in experiment
59% With iodine; dimethyl sulfoxide at 60℃; for 24h;
59% With iodine; dimethyl sulfoxide at 60℃; for 24h; Schlenk technique; 12 Example 124 - chloro -2 - -1 - hydroxy phenyl butanone Taking a 25 ml Schlenk reaction tube, iodize elemental (I2) 26 mg (0.1mmol) as catalyst, 4 - chloro -1 - phenyl butanone 92 mg (0.5mmol), dimethyl sulfoxide (DMSO) 0.5 ml as the oxidizing agent, carbonylating and solvent, for 60 °C stirring for 24 hours. After the reaction by adding ethyl acetate 15 ml, salt water 3 ml, ethyl acetate 3 times, the combined organic phase, column chromatography to obtain 4 - chloro -2 - hydroxy -1 - phenyl butanone pure product 58 mg, yield 59%.
Multi-step reaction with 2 steps 1: bromine / acetic acid / 4 h / 20 - 30 °C 2: lithium hydroxide monohydrate; water / methanol / 1 h / 20 °C
Multi-step reaction with 2 steps 1: bromine / acetic anhydride / 4 h / 20 - 30 °C 2: lithium hydroxide monohydrate / water; methanol / 1 h / 20 °C

  • 55
  • [ 1352948-14-1 ]
  • [ 939-52-6 ]
  • [ 1352949-95-1 ]
YieldReaction ConditionsOperation in experiment
41% With potassium carbonate; sodium iodide In butanone at 78℃; for 18h; 69 Preparation of tert-butyl 3-((4-oxo-8-(4-oxo-4-phenylbutyl)-l-phenyl-l,3,8-triazaspiror4.51decan-3- yl)methyl)benzoate; [0264] To a solution of teri-butyl 3-((4-oxo-l-phenyl-l,3,8-triazaspiro[4.5]decan-3- yl)methyl)benzoate (0.2 g, 0.47 mmol), potassium carbonate (0.097 g, 0.7 mmol) and sodium iodide (0.021 g, 0.14 mmol) in 2-butanone (5 mL), was added 4-chlorobutyrophenone (0.076 rriL, 0.47 mmol, d = 1.138). After stirring at 78°C for 18 hours, the reaction mixture was filtered, concentrated and isolated by preparatory TLC (10% methanol/dichloromethane) to obtain the title compound (0.11 g, 41%); MS for C35H41N3O4 m/z 568.16 (M+H)+.
  • 56
  • [ 1352949-82-6 ]
  • [ 939-52-6 ]
  • [ 1352950-40-3 ]
YieldReaction ConditionsOperation in experiment
46% With potassium carbonate; sodium iodide In butanone at 81℃; for 16h; 85 Preparation of ferf -butyl 3-((l-(4-fluorophenyl)-4-oxo-8-(4-oxo-4-phenylbutyl)-1.3.8-; [0308] A mixture of teri-butyl 3-((l-(4-fluorophenyl)-4-oxo-l,3,8-triazaspiro[4.5]decan-3- yl)methyl)benzoate (250 mg, 0.57 mmol, 1 equiv), 4-chloro-l-phenylbutan-l-one (91.3 μ, 0.57 mmol, 1 equiv), sodium iodide (34 mg, 0.23 mmol, 0.4 equiv) and potassium carbonate (158 mg, 1.14 mmol, 2 equiv) in 2-butanone was stirred at 81°C for 16 h. After cooling, the reaction mixture was filtered, concentrated in vacuo and was purified using the Biotage flash chromatography system (SNAP lOg cartridge, R/= 0.45, gradient - 1 %-10% methanol in dichloromethane) to afford the title compound (100 mg, 46%); '//NMR (400 MHz, DMSO-i/6): δ 1.53 (s, 9H); 1.59-1.63 (m, 2H); 1.82 (t, 2H, J= 7.2 and 6.4 Hz); 2.19-2.23 (m, 2H); 2.37-2.39 (m, 2H); 2.70 (d, 4H, J= 7.2 Hz); 3.02 (t, 2H, J = 6.8 and 6.4 Hz); 4.54 (s, 2H); 4.59 (s, 2H); 6.84 (bs, 2H); 7.02 (t, 2H, J= 9.6 and 8.8 Hz); 7.48-7.54 (m, 2H); 7.63 (t, 1H, J= 8 Hz); 7.79-7.84 (m, 2H); 7.95-7.98 (m, 2H); MS forC35H40FN3O4 m/z 586.5 (M+H)+.
  • 57
  • [ 1352950-60-7 ]
  • [ 939-52-6 ]
  • [ 1352951-28-0 ]
YieldReaction ConditionsOperation in experiment
50% With potassium carbonate; sodium iodide In butanone at 81℃; for 16h; 94 Preparation of (SVtert-butyl 2-(4-oxo-8-(4-oxo-4-phenylbutyl)-l -phenyl-1.3.8-triazaspiro[4.51decan- 3 -yl) -2 -phenylacetate; [0328] A mixture of (5)-tert-butyl 2-(4-oxo-l-phenyl-l,3,8-triazaspiro[4.5]decan-3-yl)-2- phenylacetate (300 mg, 0.71 mmol, 1 equiv), 4-chloro-l-phenylbutan-l-one (130 mg, 0.71 mmol, 1 equiv), sodium iodide (42.6 mg, 0.28 mmol, 0.4 equiv), and potassium carbonate (196.3 mg, 1.42 mmol, 2 equiv) in 2-butanone was stirred at 81°C for 16 h. After cooling the reaction mixture, the crude mixture was partitioned between ethyl acetate and water. The organic layer was dried over MgSO i, filtered, concentrated, and the crude residue was purified using the Biotage flash chromatography system (SNAP lOg cartridge, R/= 0.5, gradient - 1% - 10% methanol in dichloromethane) to afford the title compound as an oil (200 mg, 50%); MS for C35H41N3O4 m/z 568.4 (M+H)+.
  • 58
  • [ 939-52-6 ]
  • (R)-4-chloro-1-phenyl-1-butanol [ No CAS ]
YieldReaction ConditionsOperation in experiment
98% With borane-THF; (S)-1-methyl-3,3-diphenyl-hexahydropyrrolo[1,2-c][1,3,2]oxazaborole In tetrahydrofuran at 0℃; Inert atmosphere; optical yield given as %ee; enantioselective reaction;
With D-glucose; lyophilized cells of Escherichia coli pET28a-CpAR2-BmGDH; potassium carbonate In ethanol at 30℃; Green chemistry; enantioselective reaction;
>99 % ee With Debaryomyceshansenii carbonyl reductase N179S/I214F/S215G; NADPH In aq. phosphate buffer at 30℃; for 2h; Enzymatic reaction; stereoselective reaction;
97 % ee With bis(1,5-cyclooctadiene)diiridium(I) dichloride; C33H32FeNOP; hydrogen; potassium carbonate In ethanol; hexane at 25 - 30℃; for 12h; Inert atmosphere; Glovebox; Autoclave; enantioselective reaction;

  • 59
  • [ 102-97-6 ]
  • [ 939-52-6 ]
  • [ 1242534-30-0 ]
YieldReaction ConditionsOperation in experiment
With N-ethyl-N,N-diisopropylamine In 1,4-dioxane at 100℃; for 1.5h; 179 Example 1793-(N-isopropylbenzyl)aminopropylphenylketone 8523 4-chlorobutyrophenone (10 mg), isopropylbenzylamine (3.8 mg), and diisopropylethanol amine (4.7 mg) at 100° C. for 1.5 hours.NMR (CDCl3) 1.05 (m, 6H), 2.3 (m, 4H), 3.2 (m, 2H), 3.0 (m, 1H), 3.7 (m, 2H), 6.5 (1H), 7.5-80 (10H)TG 107 (3 μmol) 100 (10 μmol) 75 (30 μmol)SOCE 0 (10 μmol) 0 (30 μmol) 0 (100 μmol)IICR 0 (10 μmol) 0 (30 μmol) 0 (100 μmol)
  • 60
  • [ 109-56-8 ]
  • [ 939-52-6 ]
  • [ 1242534-28-6 ]
YieldReaction ConditionsOperation in experiment
With N-ethyl-N,N-diisopropylamine In 1,4-dioxane at 50℃; for 2h; 178 Example 1783-(N-isopropylhydroxyethyl)aminopropylphenylketone 8522 Chlorobutyrophenone (10.9 mg), hydroxyethylisopropylamine (3.8 mg), and diisopropylethyl amine (4 mg) were reacted in dioxane (0.2 ml) at 50° C. for 2 hours.NMR (CDCl3) 2.5 (m, 2H), 3.0 (m, 4H), 3.0 (m, 2H), 3.6 (m, 2H), 6.6 (1H), 6.5 (1H), 7.1-7.2.0 (7H)TG 107 (3 μmol) 100 (10 μmol) 60.3 (30 μmol)SOCE 0 (10 μmol) 0 (30 μmol) 0 (100 μmol)IICR 0 (10 μmol) 0 (30 μmol) 0 (100 μmol)
  • 61
  • [ 939-52-6 ]
  • [ 97505-87-8 ]
YieldReaction ConditionsOperation in experiment
25% With sodium cyanide; ammonium acetate In water; <i>tert</i>-butyl alcohol at 70℃; for 12h; 39 Production of 2-phenylpyrroline (in the above-mentioned formula (6), R1=Ph, R2=R3=H; step (a) using 4-chloro-1-phenyl-1-butanone and ammonium acetate, reaction in t-butanol-water solvent) 4-Chloro-1-phenyl-1-butanone (0.32 ml, 2 mmol), sodium cyanide (0.11 g, 2.2 mmol), ammonium acetate (0.46 g, 6 mmol), water (1 ml) and t-butanol (2 ml) were charged in a flask, and the mixture was reacted at 70°C for 12 hr. The reaction mixture was extracted with ethyl acetate, and the organic layer was dried over magnesium sulfate. The solvent was evaporated to give a pale-brown oily substance, which was purified by silica gel column chromatography to give 2-phenylpyrroline (87 mg, 0.50 mmol, yield 25%) as a pale-brown oily substance. 1H-NMR (400MHz, CDCl3) δ 2.00-2.09(2H,m), 2.92-2.99(2H,m), 4.04-4.10(2H,m), 7.38-7.44(3H,m), 7.81-7.87(2H,m).
  • 62
  • [ 773837-37-9 ]
  • [ 100-46-9 ]
  • [ 939-52-6 ]
  • [ 1415303-36-4 ]
YieldReaction ConditionsOperation in experiment
90% With acetic acid In water; <i>tert</i>-butyl alcohol at 50℃; for 9h; 40 Production of 1-benzyl-2-cyano-2-phenylpyrrolidine (in the above-mentioned formula (7), R1=Ph, R2=Bn, R3=H; step (a) using 4-chloro-1-phenyl-1-butanone, benzylamine and acetic acid, reaction in t-butanol-water solvent) 4-Chloro-1-phenyl-1-butanone (0.32 ml, 2 mmol), sodium cyanide (0.11 g, 2.2 mmol), benzylamine (0.66 ml, 6 mmol), acetic acid (0.34 ml, 6 mmol), water (1 ml) and t-butanol (1 ml) were charged in a flask, and the mixture was reacted at 50°C for 9 hr. To the reaction mixture were added 50 w/v% NaOH aqueous solution (0.48 ml) and sodium chloride, and the mixture was extracted with ethyl acetate, and the organic layer was dried over magnesium sulfate. The solvent was evaporated to give a pale-yellow oily substance (1.05 g). From the results of NMR analysis, this oily substance was a mixture containing 1-benzyl-2-cyano-2-phenylpyrrolidine (45 wt%, 0.47 g, yield 90%), benzylamine (46 wt%) and ethyl acetate (9 wt%).
90% With acetic acid In water; <i>tert</i>-butyl alcohol at 50℃; for 9h; 37 Manufacture of 1-benzyl-2-cyano 2-phenylpyrrolidine In a flask, 0.32 ml (2.0mmol) of 4-chloro-1-phenyl-1-butanone, The sodium cyanide 0.11g (2.2mmol), 0.66 ml (6.0mmol) of benzylamine, 0.34 ml (6.0mmol) of acetic acid, 1.0 ml of water, and 1.0 ml of t-butanol were prepared, and it was made to react at 50 degrees C for 9 hours. 0.48 ml of NaOH aqueous solutions and salt were added to reaction mixture 50 w/v%, ethyl acetate extracted, and it dried the organic layer with magnesium sulfate. The solvent was distilled off and the light yellow oil 1.05g was obtained.It was a mixture for which this oil contains 1-benzyl-2-cyano 2-phenylpyrrolidine 45% by weight (0.47 g, 90% of yield), and contains 46 % by weight, benzylamine, and 9 % by weight of ethyl acetate from the result of NMR analysis.
  • 63
  • [ 100-97-0 ]
  • [ 939-52-6 ]
  • [ 144513-30-4 ]
YieldReaction ConditionsOperation in experiment
26% With acetic anhydride for 18h; Reflux; Inert atmosphere; 4 4.1.4. 2-(2-Chloroethyl)-indan-1-one 4.1.4 2-(2-Chloroethyl)-indan-1-one A mixture of 4-chloro-1-phenyl-butan-1-one (10 g, 54 mmol), hexamethylene triamine (10.5 g, 75 mmol) in Ac2O (25 mL) was refluxed under N2 for 18 h. After cooling to rt, the mixture was diluted with CHCl3 (500 mL) and then washed with HCl solution (10%, 2 * 300 mL), H2O (300 mL), and saturated aq NaHCO3 (300 mL). The organic layer was dried over anhydrous Na2SO4, filtered and the filtrate was concentrated in vacuo. The residue was purified by column chromatography on silica gel to afford 4-chloro-2-methylene-1-phenyl-butan-1-one (2.8 g, 26%).
  • 64
  • [ 33553-82-1 ]
  • [ 939-52-6 ]
YieldReaction ConditionsOperation in experiment
99% With Oxone; potassium bromide In water; acetonitrile at 20℃; for 6h;
  • 65
  • [ 939-52-6 ]
  • [ 504-63-2 ]
  • 2-(3-Chloro-propyl)-2-phenyl-[1,3]dioxane [ No CAS ]
YieldReaction ConditionsOperation in experiment
With toluene-4-sulfonic acid In benzene for 10h; Reflux; Dean-Stark; Preparation of alkylating agents (IIa)-(IIm) General procedure: A solution of the phenone prepared at the previous step (10 mmol), the corresponding diol (100 mmol),and TSA (0.5 g, 2.6 mmol) were mixed in dry benzene (70 mL). The resulting solution was refluxed for 10 h using a Dean-Stark trap. The reaction mixture was cooled and a solution semisaturated sodium hydrocarbonate (50 mL) was added. The organic layer was separated, and the aqueous phase was extracted with benzene (3 × 30 mL). The united organic extracts were dried with anhydrous sodium sulfate and the solvent was evaporated. The residue was purified by column chromatography (l = 5 cm, d = 5 cm) on silica gel eluting with methylene chloride.
  • 66
  • [ 56-81-5 ]
  • [ 939-52-6 ]
  • 2-(3-chloropropyl)-2-phenyl-4-hydroxymethyl-1,3-dioxolane [ No CAS ]
YieldReaction ConditionsOperation in experiment
With toluene-4-sulfonic acid In benzene for 10h; Reflux; Dean-Stark; Preparation of alkylating agents (IIa)-(IIm) General procedure: A solution of the phenone prepared at the previous step (10 mmol), the corresponding diol (100 mmol),and TSA (0.5 g, 2.6 mmol) were mixed in dry benzene (70 mL). The resulting solution was refluxed for 10 h using a Dean-Stark trap. The reaction mixture was cooled and a solution semisaturated sodium hydrocarbonate (50 mL) was added. The organic layer was separated, and the aqueous phase was extracted with benzene (3 × 30 mL). The united organic extracts were dried with anhydrous sodium sulfate and the solvent was evaporated. The residue was purified by column chromatography (l = 5 cm, d = 5 cm) on silica gel eluting with methylene chloride.
  • 67
  • [ 35161-71-8 ]
  • [ 939-52-6 ]
  • 4-(methyl(prop-2-yn-1-yl)amino)-1-phenylbutan-1-one [ No CAS ]
YieldReaction ConditionsOperation in experiment
44% In acetonitrile at 100℃; for 1.5h; Inert atmosphere;
44% In acetonitrile at 100℃; for 1.5h; General procedure: (method D3) To the appropriate halogenated keton in ACN (200.0 mmol) was added N- methylpropargylamine (2 eq). The reaction was stirred for 1.5 h at 100 °C. The solvent was then removed under reduced pressure. The residue was purified via the Biotage SP1 silica- packed 40+M column with eluent of EtOAc:Hexane (12-50%) to afford desired compound as yellow oil. This reaction only reaches 50% (at most) conversion. Un-reacted starting material was recovered from column purification.
  • 68
  • [ 676-58-4 ]
  • [ 939-52-6 ]
  • 2-methyl-2-phenyltetrahydrofuran [ No CAS ]
YieldReaction ConditionsOperation in experiment
80% Stage #1: methylmagnesium chloride; 4-chloro-1-phenylbutan-1-one In tetrahydrofuran at -40℃; for 12h; Stage #2: With sodium hydroxide In tetrahydrofuran; water for 3h;
  • 69
  • [ 1068-55-9 ]
  • [ 939-52-6 ]
  • [ 117769-75-2 ]
YieldReaction ConditionsOperation in experiment
65% Stage #1: isopropylmagnesium chloride; 4-chloro-1-phenylbutan-1-one With choline chloride; glycerol In tetrahydrofuran at 20℃; for 0.166667h; Stage #2: With sodium hydroxide In tetrahydrofuran; water
  • 70
  • [ 2386-64-3 ]
  • [ 939-52-6 ]
  • 2-ethyl-2-phenyltetrahydrofuran [ No CAS ]
YieldReaction ConditionsOperation in experiment
75% Stage #1: ethylmagnesium chloride; 4-chloro-1-phenylbutan-1-one With choline chloride; glycerol In tetrahydrofuran at 20℃; for 0.166667h; Stage #2: With sodium hydroxide In tetrahydrofuran; water
  • 71
  • [ 699-19-4 ]
  • [ 939-52-6 ]
  • [ 1618101-91-9 ]
YieldReaction ConditionsOperation in experiment
70% Stage #1: 4-methoxyphenylmagnesium chloride; 4-chloro-1-phenylbutan-1-one With choline chloride; glycerol In tetrahydrofuran at 20℃; for 0.166667h; Stage #2: With sodium hydroxide In tetrahydrofuran; water
  • 72
  • [ 939-52-6 ]
  • [ 51833-36-4 ]
  • C16H15ClO [ No CAS ]
YieldReaction ConditionsOperation in experiment
80% Stage #1: 4-chloro-1-phenylbutan-1-one; 4-chlorophenylmagnesium chloride With choline chloride; glycerol In tetrahydrofuran at 20℃; for 0.166667h; Stage #2: With sodium hydroxide In tetrahydrofuran; water
  • 73
  • [ 917-54-4 ]
  • [ 939-52-6 ]
  • 2-methyl-2-phenyltetrahydrofuran [ No CAS ]
YieldReaction ConditionsOperation in experiment
85% Stage #1: methyllithium; 4-chloro-1-phenylbutan-1-one In tetrahydrofuran; diethyl ether at -40℃; for 12h; Stage #2: With sodium hydroxide In tetrahydrofuran; diethyl ether; water for 3h;
  • 74
  • [ 1888-75-1 ]
  • [ 939-52-6 ]
  • [ 117769-75-2 ]
YieldReaction ConditionsOperation in experiment
70% Stage #1: isopropyllithium; 4-chloro-1-phenylbutan-1-one In diethyl ether; water at 20℃; for 0.166667h; Stage #2: With sodium hydroxide In diethyl ether; water
  • 75
  • [ 811-49-4 ]
  • [ 939-52-6 ]
  • 2-ethyl-2-phenyltetrahydrofuran [ No CAS ]
YieldReaction ConditionsOperation in experiment
85% Stage #1: ethyllithium; 4-chloro-1-phenylbutan-1-one In diethyl ether; water at 20℃; for 0.166667h; Stage #2: With sodium hydroxide In diethyl ether; water
  • 76
  • [ 13139-86-1 ]
  • [ 939-52-6 ]
  • [ 1618101-91-9 ]
YieldReaction ConditionsOperation in experiment
62% Stage #1: 4-methoxyphenyl magnesium bromide; 4-chloro-1-phenylbutan-1-one In tetrahydrofuran; water at 20℃; for 0.166667h; Stage #2: With sodium hydroxide In tetrahydrofuran; water
  • 77
  • [ 873-77-8 ]
  • [ 939-52-6 ]
  • C16H15ClO [ No CAS ]
YieldReaction ConditionsOperation in experiment
58% Stage #1: (4-chlorphenyl)magnesium bromide; 4-chloro-1-phenylbutan-1-one In tetrahydrofuran; water at 20℃; for 0.166667h; Stage #2: With sodium hydroxide In tetrahydrofuran; water
  • 78
  • [ 29786-93-4 ]
  • [ 939-52-6 ]
  • 2-butyl-2-phenyl-tetrahydro-furan [ No CAS ]
YieldReaction ConditionsOperation in experiment
75% Stage #1: n-butyllithium; 4-chloro-1-phenylbutan-1-one In diethyl ether; water at 20℃; for 0.166667h; Stage #2: With sodium hydroxide In diethyl ether; water
Same Skeleton Products
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