(4E,7Z)-TERT-BUTYL 3-((Z)-3-HYDROXYPROP-1-EN-1-YL)-4,7-DIENOATE

(4E,7Z)-TERT-BUTYL 3-((Z)-3-HYDROXYPROP-1-EN-1-YL)-4,7-DIENOATE

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 (4E,7Z)-TERT-BUTYL 3-((Z)-3-HYDROXYPROP-1-EN-1-YL)-4,7-DIENOATE

 
 

 
 


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1-Aminomethyl-cyclobutyl)-acetic acid hydrochloride

EXAMPLE 2

(1) (2)

(iii), (iv)

(l-Aminomethyl-cyclobutyl)-acetic acid hydrochloride

Reagents: (i) Triethylphosphonoacetate, NaH; (ii) MeNO2, Bu4N⁺F^"; (iii) H2, Ni; (iv) HCl

Synthesis of Cyclobutylidene-acetic acid ethyl ester (2)

NaH (60%) dispersion in oil, 1.80 g, 44.94 mmol) was suspended in dry tetrahydrofuran (80 mL) and cooled to 0°C. Triethylphosphonoacetate (9.33 mL, 47.08 mmol) was added and the mixture stirred at 0°C for 15 minutes. Cyclobutanone (1) (3.0 g, 42.8 mmol) in THF (20 mL) was then added and the mixture allowed to warm to room temperature. After 2 hours, the mixture was partitioned between diethyl ether (200 mL) and water (150 mL). The organic phase was separated, washed with brine, dried (MgSO4), and the solvent removed in vacuo at 600 mm Hg. The residue was purified by flash chromatography (silica, ethyl acetate :pentane 1 : 19) to give 5.81 g (96%) of (2) as a colorless oil. iH NMR, 400 MHz (CDCI3): δ 1.27 (3H, t, J=6Hz), 2.09 (2H, m), 2.82 (2H, m),

3.15 (2H, m), 4.14 (2H, q, J = 6 Hz), 5.58 (IH, s).

MS (ES+) m/e: 141 ([MH+], 100%). IR (film) v cm"¹: 1088, 1189, 1336, 1673, 1716,2926. Synthesis of (l-Nitromethyl-cyclobutyl)-acetic acid ethyl ester (3)

The unsaturated ester (2) (5.79 g, 41.4 mmol) was dissolved in tetrahydrofuran (20 mL) and stirred at 70°C with nitromethane (4.67 mL, 86.4 mmol) and tetrabutylammonium fluoride (1.0 M in tetrahydrofuran, 55 mL, 55.0 mmol). After 18 hours, the mixture was cooled to room temperature, diluted with ethyl acetate (150 mL), and washed with 2N HCl (60 mL) followed by brine (100 mL). The organic phase was collected, dried (MgSO4), and the solvent removed in vacuo. The residue was purified by flash chromatography (silica, ethyl acetate:heptane 1 :1) to give 4.34 g (52%) of a clear oil. !H NMR 400 MHz (CDC1₃): δ 1.27 (3H, t, J = 6 Hz), 1.96-2.20 (6H, m), 2.71

(2H, s), 4.15 (2H, q, J = 6 Hz), 4.71 (2H, s).

MS (ES+) m/e: 202 ([MH+], 100%).

IR Cfiln- v cm-¹ : 1189, 1378, 1549, 1732, 2984.

Synthesis of (l-Aminomethyl-cyclobutyl)-acetic acid hydrochloride (4) The nitroester (3) (2.095 g, 10.4 mmol) was dissolved in methanol

(50 mL) and shaken over Raney nickel catalyst under an atmosphere of hydrogen (45 psi) at 30°C. After 6 hours, the catalyst was removed by filtration through celite. The solvent was removed in vacuo to give 1.53 g of a pale yellow oil which was used without purification. The oil was dissolved in 1 ,4-dioxane (5 mL) and 6N HCl (15 mL) and heated to reflux. After 5 hours, the mixture was cooled to room temperature, diluted with water (20 mL), and washed with dichloromethane (3 x 30 mL). The aqueous phase was collected and the solvent removed in vacuo. The residue was triturated with ethyl acetate to give 1.35 g (72%) of a white solid after collection and drying. ^!H NMR 400 MHz (de-DMSO): δ 1.80-2.03 (6H, m), 2.59 (2H, s), 3.02 (2H, s),

8.04 (3H, br s), 12.28 (IH, br s).

MS (ES+) m/e: 144 ([MH-HC1J+, 100%). Microanalysis calculated for C7H14NO2CI:

C, 46.80%; H, 7.86%; N, 7.80%. Found: C, 46.45%; H, 7.98%; N, 7.71%.

//////////////http://www.google.co.in/patents/WO1999021824A1?cl=en

Lithium Dicyclohexylamide - Practical and Economic Lithiations of Functionalised Arenes and Heteroarenes in Flow

The economic amide base lithium dicyclohexylamide (Cy₂NLi) allows fast and convenient (40s, 0°C) in situ trapping flow metalations of a broad range of functionalized arenes, heteroarenes and acrylate derivatives in the presence of various metal salts (ZnCl₂·2LiCl, MgCl₂, LaCl₃·2LiCl).

The resulting Zn-, Mg- or La-organometallic intermediates are trapped with various electrophiles in high yields.

These flow metalations are easily scaled-up without further optimization.

 Lithium Dicyclohexylamide - Practical and Economic Lithiations of Functionalised Arenes and Heteroarenes in Flow

M. R. Becker, M. A. Ganiek amd P. Knochel, Chem. Sci., 2015, 6, 6649

Practical and economic lithiations of functionalized arenes and heteroarenes using Cy₂NLi in the presence of Mg, Zn or La halides in a continuous flow

Matthias R. Becker,^a   Maximilian A. Ganiek^a and   Paul Knochel*^a  

*

Corresponding authors

^a

Ludwig-Maximilians-Universität München, Department Chemie, Butenandtstrasse 5-13 (Haus F), 81377 München, Germany
E-mail: paul.knochel@cup.uni-muenchen.de

Chem. Sci., 2015,6, 6649-6653

DOI: 10.1039/C5SC02558C
 http://pubs.rsc.org/en/content/articlelanding/2015/sc/c5sc02558c#!divAbstract


 The economic amide base lithium dicyclohexylamide (Cy₂NLi) allows fast and convenient (40 s, 0 °C) in situ trapping flow metalations of a broad range of functionalized arenes, heteroarenes and acrylate derivatives in the presence of various metal salts (ZnCl₂·2LiCl, MgCl₂, LaCl₃·2LiCl). The resulting Zn-, Mg- or La-organometallic intermediates are trapped with various electrophiles in high yields. These flow metalations are easily scaled-up without further optimization.


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Asymmetric phase transfer catalysis has been recognized as an approach that is greener and more sustainable than synthetic alternatives and has evolved into one of the most practical methods in challenging enantioselective synthesis. An overview of the current status of asymmetric phase transfer catalysis in industry is presented by summarizing research progress from both journal publications and patent applications.

 

Contemporary Asymmetric Phase Transfer Catalysis: Large-Scale Industrial Applications

Jiajing Tan^* and Nobuyoshi Yasuda

Department of Process Chemistry, Merck and Co., Inc., P.O. Box 2000, Rahway, New Jersey 07065, United States

Org. Process Res. Dev., Article ASAP

DOI: 10.1021/acs.oprd.5b00304

Publication Date (Web): September 29, 2015

Copyright © 2015 American Chemical Society

*E-mail: jiajing.tan@merck.com.

 http://pubs.acs.org/doi/abs/10.1021/acs.oprd.5b00304

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A manganese catalyst for highly reactive yet chemoselective intramolecular C( sp 3 ) – Hamination

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A manganese catalyst for highly reactive yet chemoselective intramolecular C(sp3)–H amination

 http://urlaa.com/Manganese-Catalyst-CH-activation.pdf

http://bit.ly/1LuzWSU 

A 10 million times more abundant metal than rhodium, Manganese within a complex showed high reactivity and in the same time high selectivity to make precious molecules that can speed up Drug development. #manganesecomplex #catalyst #drugdiscovery #drugdevelopment

An odorless, one-pot synthesis of nitroaryl thioethers via SNAr reactions through the in situ generation of S-alkylisothiouronium salts

A newly developed C–S bond formation nucleophilic aromatic substitution (S_NAr) reaction in aqueous Triton X-100 (TX100) micelles has been disclosed. This chemistry, in which odorless, cheap and stable thiourea in place of thiols is used as the sulfur reagent, provides an efficient approach for the generation of nitroaryl thioethers, which are useful structural units of many bioactive molecules, rendering this methodology attractive to both synthetic and medicinal chemistry.

An odorless, one-pot synthesis of nitroaryl thioethers via S_NAr reactions through the in situ generation of S-alkylisothiouronium salts

Guo-ping Lu*^a and   Chun Cai^a  

*Corresponding authors

^aChemical Engineering College, Nanjing University of Science & Technology, Nanjing, P. R. China
E-mail: glu@njust.edu.cn

RSC Adv., 2014,4, 59990-59996

DOI: 10.1039/C4RA11490F

http://pubs.rsc.org/en/content/articlelanding/2014/ra/c4ra11490f#!divAbstract
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