(5-Chloro-2-methoxyphenyl)[3-fluoro-5-(trifluoromethyl)phenyl]methanone

Cas 329941-92-6

C15 H9 Cl F4 O2

Methanone, (5-chloro-2-methoxyphenyl)[3-fluoro-5-(trifluoromethyl)phenyl]-

(5-Chloro-2-methoxyphenyl)[3-fluoro-5-(trifluoromethyl)phenyl]methanone (7)

7 as white crystals

 

mp 93–95 °C;

 

1H NMR (500 MHz, CDCl3) 7.82 (s, 1H), 7.66 (d, J = 8.5 Hz, 1H), 7.53 (d, J =7.5 Hz, 1H), 7.49 (d, J = 9.0 Hz, 1H), 7.42 (s, 1H), 6.97 (d, J = 9.0 Hz, 1H), 3.71 (s, 3H);

 

13C NMR (500 MHz, CDCl3) 192.1, 162.4 (d, J = 249.3 Hz), 156.0, 140.4 (d, J = 6.4 Hz), 132.8, 132.7 (dq, J = 7.5, 33.6 Hz), 129.7, 128.4, 126.3, 122.9 (q, J = 272.3), 122.1 (m), 119.5 (d, J = 22.4), 116.9 (m), 113.3, 55.3;

 

HRMS calculated for C15H9ClF4O2 [M + H]+: 333.0299, Found: 333.0306.

 

A convergent synthesis of NNRTI 1 is described. The key step involves a direct coupling of acid chloride 4 with Grignard reagent 11 in the presence of bis[2-(N,N-dimethylamino)ethyl] ether that moderates the reactivity of the Grignard reagent to give benzophenone 7. An efficient 2-step process for the preparation of 2-fluoro-3-methyl-4-aminobenzoic acid (3) is also described.

Practical Synthesis of A Benzophenone-Based NNRT Inhibitor of HIV-1

Xiao-jun Wang*†, Li Zhang†, Xiufeng Sun†, Heewon Lee†, Dhileepkumar Krishnamurthy†, Jeff A. O’Meara‡, Serge Landry‡, Christiane Yoakim‡, Bruno Simoneau‡, Nathan K. Yee†, and Chris H. Senanayake†

† Chemical Development, Boehringer Ingelheim Pharmaceuticals Inc., Ridgefield, Connecticut 06877, United States

‡ Boehringer Ingelheim (Canada) Ltd., Research and Development, 2100 Cunard Street, Laval, Québec H7S 2G5, Canada

Org. Process Res. Dev., 2012, 16 (4), pp 561–566

DOI: 10.1021/op200301h

 

*E-mail: xiao-jun.wang@boehringer-ingelheim.com.

http://pubs.acs.org/doi/suppl/10.1021/op200301h

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tert-butyl(3aR,6aS)-5-oxohexahydrocyclopenta[c]pyrrole-2(1H)-carboxylate

tert-butyl(3aR,6aS)-5-oxohexahydrocyclopenta[c]pyrrole-2(1H)-carboxylate

   

tert-Butyl (3aR,6aS)-5-Oxohexahydrocyclopenta[c]pyrrole-2(1H)-carboxylate (1)

pure compound 1 (1.051 kg, 67%) as a white solid. Mp: 70–71 °C (uncorrected); [α]²⁵_D +0.40° (c 1.00 CHCl₃); % purity: 98.5% (HPLC);

 

¹H NMR (CDCl₃, 400 MHz) δ: 1.46 (s, 9H), 2.15 (dd, J₁ = 4.8 Hz, J₂ = 19.6 Hz, 2H), 2.47 (dd, J₁ = 7.4 Hz, J₂ = 19.6 Hz, 2H), 2.93 (bs, 2H), 3.16–3.28 (m, 2H), 3.65–3.67 (m, 2H).;

 

¹³C NMR (CDCl₃, 100 MHz) δ: 38.49, 39.36, 42.32, 50.51, 50.77, 79.49, 154.39, 217.65; IR (KBr): ν = 638, 771, 877, 1118, 1166, 1247, 1367, 1402, 1691, 1741, 2877, 2910, 2958, 2976, 3005 cm^–1;

 

TOFMS: [C₁₂H₁₉NO₃ + H⁺]: calculated 226.1438, found 152.0663 (M-OtBu)⁺ (100%), 170.0755 (M-tBu + H)⁺ (40%), 248.1166 (M + Na)⁺ (5%).

 

Anal. Calcd for C₁₂H₁₉NO₃: C, 63.98; H, 8.50; N, 6.22. Found: C, 63.89; H, 8.27; N, 5.97.

HPLC conditions were as follows for compound ; Agilent 1100 series, column: YMC J’SPHERE C18 (150 mm X 4.6 mm) 4µm with mobile phases A (0.05% TFA in water) and B (acetonitrile). Detection was at 210 nm, flow was set at 1.0 mL/min, and the temperature was 30 °C (Run time: 45 min). Gradient: 0 min, A = 90%, B = 10%; 5.0 min, A = 90%, B = 10%; 25 min, A = 0%, B = 100%; 30 min, A = 0%, B = 100%, 35 min, A = 90%, B = 10%; 45 min, A = 90%, B = 10%.

Org. Process Res. Dev., Article ASAP

DOI: 10.1021/acs.oprd.6b00399

http://pubs.acs.org/doi/full/10.1021/acs.oprd.6b00399

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(S,S,S)-2-aza-bicyclo-[3.3.0]- octane-3-carboxylic acid benzyl ester, Ramipril intermediate

93779-31-8 cas

Cyclopenta[b]pyrrole-2-carboxylicacid, octahydro-, phenylmethyl ester, (2S,3aS,6aS)-

Formula:	C15H20ClNO2
Molecular Weight:	281.78

cas 93779-29-4

(S,S,S)-2-aza-bicyclo-[3.3.0]- octane-3-carboxylic acid benzyl ester

(S,S,S)-2-aza-bicyclo-[3.3.0]- octane-3-carboxylic acid benzyl ester, white solid. Yield 33.7 g (95%); mp 178–180 8C (lit.[6c] mp 180 8C); [a]D 20 ¼ 240.0 (c ¼ 1, H2O) [lit.[6c] [a]D 30 ¼ 238.4 (c ¼ 1, H2O)];

 1H NMR (400 MHz, CDCl3) d 1.36–1.42 (m, 1H), 1.58–1.75 (m, 2H), 1.82–2.01 (m, 3H), 2.32–2.37 (m, 1H), 2.58 (dt, J ¼ 13.2, 8.4 Hz, 1H), 2.83–2.88 (m, 1H), 4.31 (td, J ¼ 8.0, 3.6 Hz, 1H), 4.43 (t, J ¼ 8.4 Hz, 1H), 5.20 (AB q,J ¼ 12.0 Hz, 2H), 7.33–7.37 (m, 5H); 13C NMR (50 MHz, DMSO) d 24.07, 29.60, 31.02, 33.45, 41.37, 60.11, 63.81, 66.99, 128.11, 128.28, 128.43, 135.14, 167.32; FT IR (KBr disc) 1758 cm21; MS: m/e 246 (Mþ).

(c) Teetz, V.;
Geiger, R.; Gaul, H. Synthesis of unnatural amino acids: (S,S,S)-2-azabicyclo-
[3.3.0]-octane-3-carboxylic acid. Tetrahedron Lett. 1984, 25, 4479.

(3aS, 6aR)-3-Oxyhexahydrofuro [2, 3-b] furan

(3aS, 6aR)-3-Oxyhexahydrofuro [2, 3-b] furan

809286-93-9 cas

[ Molecular Formula ]:	C6H8O3
[ Molecular Weight ]:	128.12600

(6): Under a nitrogen atmosphere, a, solution containing 440 mg (3.38 mmol) (3S, 3aS, 6aR)-3-hydroxy-hexahydrofuro [2, 3-b] furan (5), 599 mg (5.11 mmol) 4-methylmorpholine-N-oxide, and 2 g 4 A molecular sieves in CH₂Cl₂ (30 mL) was stirred for 20 minutes. Then, tetrapropylammonium perruthenate (36 mg (0.10 mmol)) was added at room temperature. After 5-10 minutes, the reaction mixture was filtered through a pad of silica gel (5 g) with CH₂Cl₂ (100 mL). After evaporation, column chromatography (silica gel 70 g, ethyl acetate in hexanes 40%) gave compound (6) (409 mg. 94%) as a colorless solid, R_f=0.3, [α]²⁵_D -126.6°, c 0.8, CHCl₃, 

IR (Neat) 1758, 1658, 1023 cm^-1;

 ¹H-NMR (400 MHz, CDCl₃) δ: 2.23 (m_c, 1H), 2.96 (dd, 1H, J=6.8 Hz, J=6.8 Hz), 3.79 (m_c, 1H), 3.99 (m, 1H), 4.11 (s, 2H), 6.02 (d, 1H, J=5.0 Hz).

 ¹³C-NMR (100.6 MHz, CDCl₃, Dept) δ: 30.38 (-), 49.58 (+), 67.65 (-), 71.69 (-), 107.89 (+), 215.52 (quat). 

C₆H₈O₃;

Exact Mass: 128.05; Mol. Wt.: 128.13; C, 56.24, H, 6:29, 0, 37.46.

https://www.google.com/patents/US20040127727

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( E ) - dimethyl octadec - 9 - enedioate

Kumbhalgarh Fort, rajasthan, india

Kumbhalgarh Fort is a Mewar fortress on the westerly range of Aravalli Hills, in the Rajsamand District of Rajasthan state in western India. It is a World Heritage Site included in Hill Forts of Rajasthan. Wikipedia

Address: Rajasthan

 

 
 

 
 
 
 
 
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