N‒(4’‒methoxyCinnamyl)aniline ( NMR IS EASY)

N‒(4’‒methoxyCinnamyl)aniline

N‒(4'‒Methoxycinnamyl)aniline (3s): Yellow brown solid (203 mg, 85% yield),

mp. 75 oC,

1H NMR (CDCl3, 600 MHz): δ 3.86 (s, 3H), 3.94 (d, 2H, J = 11.5 Hz), 6.20‒ 6.29 (m, 1H), 6.60 (d, 1H, J = 15.9 Hz), 6.74 (d, 2H, J = 8.28 Hz), 6.80 (t, 1H, J = 6.9 Hz), 6.93 (d, 2H, J = 4.32 Hz), 7.24‒7.29 (m, 2H), 7.38 (d, 2H, J = 8.6 Hz);

13C NMR (CDCl3, 150 MHz): δ 46.7, 55.7, 113.5, 114.4, 117.9, 125.2, 127.9, 129.7, 130.1, 131.5, 148.6, 159.6;

HRESIMS calcd for C16H18NO [M+H]+ 240.1388, found 240.1378.

EVEN MOM CAN TEACH U NMR

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3-Phenylpropionic acid

3-Phenylpropionic acid (2z) 1

1) Jiang, X.; Zhang, J.; Ma. S. J. Am. Chem. Soc. 2016, 138, 8344

Yield: 94% (142 mg), white solid. Melting point: 47-49 °C (lit.18 49 °C)

(18) Helavi, V. B.; Solabannavar, S. B.; Desai, U. V.; Mane, R. B. J. Chem. Research 2003, 3, 174.

1 H NMR (400 MHz, CDCl3) δ 7.34 – 7.17 (m, 5H), 2.97 (t, J = 7.8 Hz, 2H), 2.69 (t, J = 7.8 Hz, 2H).

13C NMR (101 MHz, CDCl3) δ 179.82, 140.28, 128.71, 128.41, 126.52, 35.64, 30.73

1H AND 13C NMR PREDICT

Aerobic Oxidation of Diverse Primary Alcohols to Carboxylic Acids with a Heterogeneous Pd–Bi–Te/C (PBT/C) Catalyst

Maaz S. Ahmed†, David S. Mannel‡, Thatcher W. Root‡ , and Shannon S. Stahl*† 

†Department of Chemistry and ‡Department of Chemical and Biological Engineering, University of Wisconsin-Madison, Madison, Wisconsin 53706, United States

Org. Process Res. Dev., Article ASAP

DOI: 10.1021/acs.oprd.7b00223

 

*E-mail: stahl@chem.wisc.edu.

Maaz Ahmed

PhD Candidate in the Stahl Lab at University of Wisconsin-Madison

Prof. Shannon S. Stahl

Department of Chemistry
University of Wisconsin-Madison
1101 University Avenue
Madison , Wisconsin 53706
Tel: (608) 265-6288
Fax: (608) 262-6143
stahl@chem.wisc.edu
Room 6132a Chemistry

Abstract

Heterogeneous catalytic aerobic oxidation methods represent a near-ideal approach for the conversion of primary alcohols to carboxylic acids. Here, we report that a heterogeneous catalyst composed of Pd, Bi, and Te supported on activated carbon is highly effective for the oxidation of diverse benzylic and aliphatic primary alcohols, including 5-(hydroxymethyl)furfural (HMF) and substrates bearing heterocycles and other important functional groups. In many cases, the desired carboxylic acid product is obtained in >90% yield. Additionally, the catalyst has been demonstrated in a continuous-flow packed-bed reactor for the oxidation of benzyl alcohol, achieving near-quantitative yield while undergoing over 30 000 turnovers.

http://pubs.acs.org/doi/suppl/10.1021/acs.oprd.7b00223/suppl_file/op7b00223_si_001.pdf

DATA FROM OTHER SOURCES.........

Experiments:

1. 1D-1H: Peaks_list 2. 2D-[1H,1H]-TOCSY: 3. 1D-13C: Peaks_list 4. 1D-13C DEPT90: Peaks_list 5. 1D-13C DEPT135: Peaks_list 6. 2D-[1H,13C]-HSQC: Peaks_list 7. 2D-[1H,13C]-HMBC: 8. 2D-[1H,1H]-COSY:

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syn-3,5-Dihydroxy Hexanoate

pure 8 (2.4 g, HPLC purity, 92%). [α]D25 = −41.3 (c = 1.0, CHCl3), >99.5% de.(8g, 9) 1H NMR (CDCl3, 400 MHz), δ/ppm: 1.47 (s, 9H), 1.71–1.75 (m, 2H), 2.42–2.44 (m, 2H), 2.54–2.56 (m, 2H), 3.71 (brs, 2H), 4.18–4.22 (m, 1H), 4.26–4.31 (m, 1H).

t-butyl 6-cyano-(5R)-hydroxy-3-oxo-hexanoate

t-Butyl-6-cyano-(3R,5R)-dihydroxyhexanoate is an advanced chiral precursor for the synthesis of the side chain pharmacophore of cholesterol-lowering drug atorvastatin. Herein, a robust carbonyl reductase (LbCR) was newly identified from Lactobacillus brevis, which displays high activity and excellent diastereoselectivity toward bulky t-butyl 6-cyano-(5R)-hydroxy-3-oxo-hexanoate (7). The engineered Escherichia coli cells harboring LbCR and glucose dehydrogenase (for cofactor regeneration) were employed as biocatalysts for the asymmetric reduction of substrate 7. As a result, as much as 300 g L–1 of water-insoluble substrate was completely converted to the corresponding chiral diol with >99.5% de in a space–time yield of 351 g L–1 d–1, indicating a great potential of LbCR for practical synthesis of the very bulky and bi-chiral 3,5-dihydroxy carboxylate side chain of best-selling statin drugs.

Identification of a Robust Carbonyl Reductase for Diastereoselectively Building syn-3,5-Dihydroxy Hexanoate: a Bulky Side Chain of Atorvastatin

Xu-Min Gong† , Gao-Wei Zheng*† , You-Yan Liu‡§, and Jian-He Xu*†

† State Key Laboratory of Bioreactor Engineering, Shanghai Collaborative Innovation Center for Biomanufacturing, East China University of Science and Technology, 130 Meilong Road, Shanghai 200237, P. R. China

‡ School of Chemistry and Chemical Engineering, Guangxi University, Nanning 530004, Guangxi, P. R. China

§ Guangxi Key Laboratory of Biorefinery, Guangxi Academy of Sciences, Nanning 530003, Guangxi, P. R. China

Org. Process Res. Dev., Article ASAP

DOI: 10.1021/acs.oprd.7b00194

 

*E-mail: gaoweizheng@ecust.edu.cn; fax: (+86)-21-64250840., *E-mail: jianhexu@ecust.edu.cn; fax: (+86)-21-64252498.

(S)-5-fluoro-3-methylisobenzofuran-1(3H)-one

Preparation of (S)-5-Fluoro-3-methylisobenzofuran-1(3H)-one (6)

To a ................... Purity 99.9%, ee > 99.9%.

 

1H NMR (400 MHz, CDCl3): δ 7.88 (dd, J = 4.8, 8.4 Hz, 1 H), 7.21 (ddd, J = 2.0, 8.4, 8.8 Hz, 1 H), 7.12 (dd, J = 2.0, 8.8 Hz, 1 H), 5.53 (q, J = 6.4 Hz, 1 H), 1.63 (d, J = 6.4 Hz, 3 H) ppm;

 

13C NMR (100.6 MHz, CDCl3): δ 169.1, 166.5 (d, JCF = 256.6 Hz), 153.8 (d, JCF = 9.1 Hz), 128.0 (d, JCF = 10 Hz), 121.8, 117.2 (d, JCF = 24.1 Hz), 108.9 (d, JCF = 25.2 Hz), 77.0, 20.2 ppm;

 

19F NMR (376.5 MHz, CDCl3): δ −102.8 ppm.

 

HRMS: Calcd for C9H8O2F (M + H)+: 167.0503. Found: 167.0497.

Developing an Asymmetric Transfer Hydrogenation Process for (S)-5-Fluoro-3-methylisobenzofuran-1(3H)-one, a Key Intermediate to Lorlatinib

Shengquan Duan* , Bryan Li, Robert W. Dugger, Brian Conway, Rajesh Kumar, Carlos Martinez, Teresa Makowski, Robert Pearson, Mark Olivier, and Roberto Colon-Cruz

Chemical Research and Development and Analytical Research and Development, Pfizer Worldwide Research and Development, Eastern Point Road, Groton, Connecticut 06340, United States

Org. Process Res. Dev., Article ASAP

DOI: 10.1021/acs.oprd.7b00187

 

*E-mail: Shengquan.duan@pfizer.com.

 

Synthesis of (S)-5-fluoro-3-methylisobenzofuran-1(3H)-one (6), a key intermediate to lorlatinib, is described. A few synthetic methodologies, that is, boron reduction, enzymatic reduction, asymmetric hydrogenation, and asymmetric transfer hydrogenation, were evaluated for the chiral reduction of the substituted acetophenone intermediate (8). A manufacturing process, on the basis of the asymmetric transfer hydrogenation, was developed. This process was successfully scaled up to prepare 400 kg of 6.

   

1H AND 13C NMR PREDICT