31P spectrum

    This is the ³¹P spectrum. The scale is Hz. This spectrum shows the expected septuplet pattern of peaks having integrated intensities of 1:6:15:20:15:6:1 resulting from the splitting of the phosphorous atom by the six equivalent I=1/2 ¹⁹F nuclei. The coupling constant, J_PF was found experimentally to be 714 Hz, very similar to the value listed above.
The ¹⁹F and ³¹P FT-NMR Spectra This is the Free Induction Decay Curve for the ¹⁹F spectrum. This is the ¹⁹F spectrum. The scale is Hz. This spectrum shows the expected doublet pattern of peaks having equal integrated intensities resulting from the splitting of the six equivalent flourine atoms by the I=1/2 ³¹P nucleus. The coupling constant, J_PF was found experimentally to be 717 Hz. This is the ³¹P spectrum. The scale is Hz. This spectrum shows the expected septuplet pattern of peaks having integrated intensities of 1:6:15:20:15:6:1 resulting from the splitting of the phosphorous atom by the six equivalent I=1/2 ¹⁹F nuclei. The coupling constant, J_PF was found experimentally to be 714 Hz, very similar to the value listed above. The Vibrational Spectrum This vibrational spectrum was calculated by Hyperchem. The vibrations predicted by Hyperchem are at (in cm^-1): 219, 376, 470, 851, 974, and 1292. These correspond to the following examples of normal modes of vibration (in respective order):

v₆ (t_2u)                                            v₅ (t_2g) 

v₄ (t_1u)                                             v₂ (e_g) 

v₁ (a_1g)                                          v₃ (t_1u) 

In comparison with literature values from Kazuo Nakamoto's Infrared and Raman Spectra of Inorganic and Coordination Compounds; 5th ed.; Part A; page 216, these vibrations are at (in cm^-1): not available, 480~468, 559;530, 585;570, 756, and 865;835. Note the splitting of three of the spectral lines. It appears that many Hyperchem lines were calculated higher than the experimental values. This is consistent with the nature of these semi-empirical calculations (AM1). The symmetry labels above were obtained through comparison of the Hyperchem normal modes with those found in Nakamoto, p. 215. These modes were found by Hyperchem to be triply degenerate with the exceptions of v₃ (t_1u) and v₁ (a_1g) which were doubly and nondegenerate, respectively. The Electronic Spectrum This electronic spectrum of the singly excited state was calculated by Hyperchem. Note that all transitions are deep in the UV. DRUG APPROVALS BY DR ANTHONY MELVIN CRASTO .....FOR BLOG HOME CLICK HERE

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Acetonide

with 2.2 g of the p-nitrophenyl glycoside, 50 mL of 1,4-dioxane, 8 mL of 2,2-dimethoxypropane and 75 mg of TsOH.





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vietnam

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 dalat city
hanoi











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Protection of Acetol as THP ether

Protection of Acetol as THP ether

 

Protection of Acetol as THP ether

 

Literature References

1. Xiao, Y.; Liu, P. Angew. Chem. Int. Ed. 2008, 47, 9722-9725.
   • See the supplemental material for a "Synthesis of acetonyl tetrahydropyranyl ether (17)".
2. Sondheimer, F.; Stjernstrom, N.; Rosenthal, D. J. Org. Chem. 1959, 24, 1280-1284.
   • Look for the experimental for "Acetol 2'-tetrahydropyranyl ether (VIIIb)". Interestingly, they say that the material was stored at -10 degrees C, or used directly for the next step since it decomposed on standing at room temperature!
3. Hagiwara, H.; Uda, H. J. Chem. Soc., Perkin-I 1984, 91.

  The literature listing for the NMR (Xiao reference above) is ¹H-NMR (CDCl₃, 400 MHz): 4.64 (t, J = 3.6 Hz, 1 H), 4.26 (d, J = 17.6 Hz, 1 H), 4.12 (d, J = 17.6 Hz, 1 H), 3.81-3.86 (m, 1 H), 3.49-3.54 (m, 1 H), 2.18 (s, 3 H), 1.61-1.89 (m, 6 H).

1. 
   

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Ketal

.............


     

Literature References

1. Cornish, C.A.; Warren, S. J. Chem. Soc. Perkin Trans. I 1985, 2585. "Synthesis of Single Isomers (E or Z) of Protected gamma,delta-Unsaturated Ketones by the Horner-Wittig Reaction"
   • This article has procedures for the conversion of acetylbutyrolactone into the chloro, bromo, and iodo-pentanones, along with their subsequent conversions to the ethylene ketals.
2. Bellas, T.E.; Brownlee, R.G.; Silversteing, R.M. Tetrahedron 1969, 25, 5149. "Synthesis of Brevicomin, Principal Sex Attractant in the Frass of the Female Western Beetle"
• This article has an experimental for the conversion of acetylbutryolactone into 5-bromo-2-pentanone (1) and then conversion of this to ketal 2.

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WO2011069761

 






Example 2
2-(Difluoromethyl)-4-(6-fluoro-3-methyl-lH-indazol-5-yl)-6-(4-fluorophenyl)-l,4-dihydropyridine- 3,5-dicarbonitrile

A mixture of 200 mg (0.569 mmol) (2ii)-2-(4-fluorobenzoyl)-3-(6-fluoro-3-methyl-lH-indazol-5-yl)- prop-2-enenitrile (Example 5A) and 69 mg (0.569 mmol) 3-amino-4,4-difluorobut-2-enenitrile [obtainable by Thorpe reaction of acetonitrile with 2,2-difluoroacetonitrile, cf. Org. React. 15, 1 (1967), ibid. 3J_, 1 (1984)] in 2-propanol (1 ml) was stirred at reflux for 12 h. Then, acetic acid (1.5 ml) was added, and stirring at reflux was continued for 6 h. Upon cooling, the mixture was concentrated under reduced pressure, and the residue was directly purified by preparative RP-HPLC (methanol/water + 0.1 % TFA gradient, final mixture 80:20 v/v) to yield 36 mg (15% of th.) of the racemic title compound. LC-MS (method 4): R_t = 0.97 min; MS (ESIpos): m/z = 424 (M+H)
'H-NMR (400 MHz, DMSO-dg): δ = 12.87 (br. s, 1H), 10.44 (s, 1H), 7.78 (d, 1H), 7.61 (m, 2H), 7.41-7.35 (m, 3H), 6.79 (t, 1H, _F = 51.8 Hz), 5.08 (s, 1H), 2.54 (s, 3H) ppm.


 http://www.google.com/patents/WO2011069761A1?cl=en

 


Comparative Example B
2-(4-Fluorophenyl)-6-methyl-4-(3-methyl-lH-indazol-5-yl)-l,4-dihydropyridine-3,5-dicarbonitrile

A mixture of 200 mg (0.89 mmol) (2i?)-2-[(3-methyl-lH-indazol-5-yl)methylidene]-3-oxobutane- nitrile (Example 2A), 159 mg (0.98 mmol) 3-(4-fluorophenyl)-3-oxopropanenitrile and 205 mg (2.66 mmol) ammonium acetate in ethanol/acetic acid (4: 1 v/v, 1 1 ml) was heated to reflux overnight. After cooling, the reaction mixture was directly purified by preparative RP-HPLC (acetonitrile/water + 0.1% TFA gradient) to afford 136 mg (41% of th.) of the racemic title compound.
LC-MS (method 2): R_t = 1.04 min; MS (ESIpos): m/z = 370 (M+H)⁺
'H-NMR (400 MHz, DMSO-dg): δ = 12.70 (br. s, 1H), 9.74 (s, 1H), 7.64-7.59 (m, 3H), 7.53 (d, 1H), 7.40-7.33 (m, 3H), 4.68 (s, 1H), 2.48 (s, 3H), 2.11 (s, 3H) ppm.










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