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[ CAS No. 176251-49-3 ] {[proInfo.proName]}

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3d Animation Molecule Structure of 176251-49-3
Chemical Structure| 176251-49-3
Chemical Structure| 176251-49-3
Structure of 176251-49-3 * Storage: {[proInfo.prStorage]}
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Product Details of [ 176251-49-3 ]

CAS No. :176251-49-3 MDL No. :MFCD11847478
Formula : C8H12F2O2 Boiling Point : -
Linear Structure Formula :- InChI Key :FLSBLABUGHZWBS-UHFFFAOYSA-N
M.W : 178.18 Pubchem ID :22225014
Synonyms :

Calculated chemistry of [ 176251-49-3 ]

Physicochemical Properties

Num. heavy atoms : 12
Num. arom. heavy atoms : 0
Fraction Csp3 : 1.0
Num. rotatable bonds : 0
Num. H-bond acceptors : 4.0
Num. H-bond donors : 0.0
Molar Refractivity : 38.69
TPSA : 18.46 Ų

Pharmacokinetics

GI absorption : High
BBB permeant : Yes
P-gp substrate : Yes
CYP1A2 inhibitor : No
CYP2C19 inhibitor : No
CYP2C9 inhibitor : No
CYP2D6 inhibitor : No
CYP3A4 inhibitor : No
Log Kp (skin permeation) : -6.28 cm/s

Lipophilicity

Log Po/w (iLOGP) : 2.18
Log Po/w (XLOGP3) : 1.56
Log Po/w (WLOGP) : 2.78
Log Po/w (MLOGP) : 1.62
Log Po/w (SILICOS-IT) : 2.62
Consensus Log Po/w : 2.15

Druglikeness

Lipinski : 0.0
Ghose : None
Veber : 0.0
Egan : 0.0
Muegge : 1.0
Bioavailability Score : 0.55

Water Solubility

Log S (ESOL) : -1.93
Solubility : 2.11 mg/ml ; 0.0118 mol/l
Class : Very soluble
Log S (Ali) : -1.56
Solubility : 4.93 mg/ml ; 0.0277 mol/l
Class : Very soluble
Log S (SILICOS-IT) : -2.11
Solubility : 1.37 mg/ml ; 0.00771 mol/l
Class : Soluble

Medicinal Chemistry

PAINS : 0.0 alert
Brenk : 0.0 alert
Leadlikeness : 1.0
Synthetic accessibility : 2.93

Safety of [ 176251-49-3 ]

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 [ 176251-49-3 ]

* 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.

  • Upstream synthesis route of [ 176251-49-3 ]
  • Downstream synthetic route of [ 176251-49-3 ]

[ 176251-49-3 ] Synthesis Path-Upstream   1~4

  • 1
  • [ 176251-49-3 ]
  • [ 22515-18-0 ]
YieldReaction ConditionsOperation in experiment
71% With hydrogenchloride In water at 100℃; for 3 h; 4.3. 4,4-Difluorocyclohexanone (8) A suspension of ketal 7 (20.0 g, 112.2 mmol) in 20percent aq HCl (16 mL) was vigorously stirred at 100 °C for 3 h. After cooling to a room temperature NaCl (ca. 3 g) was dissolved in thewater phase. The water phase was then extracted with CH2Cl2 (3 50 mL). The combined organic phase was washed with water (50 mL), dried over Na2SO4 and slowly evaporated under reduced pressure at 20 °C. The product is very volatile. The formed material was a 1:1 mixture of product 8 and starting material 5. After repeating the above described cycle, the obtained material was 8/5=7:3. The product of 95percent purity (8) was obtained after repeating the described above procedure for five times in total. White crystalline (11.0 g, 71percent yield). Mp 31-32 °C.
Reference: [1] Organic Letters, 2013, vol. 15, # 5, p. 1088 - 1091
[2] Tetrahedron, 2013, vol. 69, # 20, p. 4066 - 4075
[3] Patent: US2006/293392, 2006, A1, . Location in patent: Page/Page column 51
[4] Patent: WO2008/7930, 2008, A1, . Location in patent: Page/Page column 28
[5] Patent: WO2009/48547, 2009, A1, . Location in patent: Page/Page column 40
[6] Patent: US2010/120783, 2010, A1, . Location in patent: Page/Page column 10
[7] Patent: WO2010/56022, 2010, A2, . Location in patent: Page/Page column 23
[8] Patent: EP2786986, 2014, A2, . Location in patent: Paragraph 0125-0127
  • 2
  • [ 4746-97-8 ]
  • [ 176251-49-3 ]
YieldReaction ConditionsOperation in experiment
73%
Stage #1: With morpholinosulfur trifluoride In dichloromethane at 0 - 20℃; for 72 h; Inert atmosphere
Stage #2: With potassium permanganate In dichloromethane; water for 24 h;
Method B
A solution of ketone 6 (4.40 g, 28.2 mmol) in dry CH2Cl2 (100 mL) was cooled to 0 °C under argon atmosphere. Morph-DAST (11.85 g, 67.7 mmol, 2.4 equiv) was added dropwise upon stirring.
The reaction mixture was allowed to warm to a room temperature and was stirred for 72 h.
A saturated solution of NaHCO3 in water (50 mL) was added and the reaction mixture was stirred for 10 min to quench the unreacted fluorinating agent.
The organic layer was separated and the water phase was extracted with CH2Cl2 (2*50 mL).
Solution of KMnO4 (5.7 g, 36 mmol, 10 equiv) in water (100 mL) was added to the combined organic phase and the formed suspension was vigorously stirred for 24 h.
The organic layer was separated and the water phase was extracted with CH2Cl2 (2*100 mL).
The combined organic phases were dried over Na2SO4, and evaporated under vacuum at 30 °C to provide pure compound 7 (3.65 g, 20.5 mmol, 73percent yield) as a colourless oil, which crystallized upon storage.
60% With (diethylamino)sulfur trifluoride In dichloromethane; water EXAMPLE 46
8,8-Difluoro-1,4-dioxa-spiro[4.5]decane
1,4-Dioxa-spiro[4.5]decan-8-one (9.0 g, 56 mmol) and (diethylamino)sulfur trifluoride (19 g, 112 mmol) are reacted in dichloromethane (180 ml) for 2 h at room temperature.
The mixture is poured in water (300 ml), the layers are separated and the aqueous phase back-extracted twice with dichloromethane (50 ml).
The combined organic phases are dried with magnesium sulfate and evaporated.
Distillation under reduced pressure over a vigreux-column afforded the title compound as colorless liquid (6.0 g, 60percent), bp 65-72° C. at 13-14 mbar, MS: m/e=186 (M+), contaminated with ~30percent 8-Fluoro-1,4-dioxa-spiro[4.5]dec-7-ene, MS: m/e=158 (M+).
45% With N-methyl-N-phenylaminodifluorosulfiniumtetrafluoroborate; triethylamine tris(hydrogen fluoride) In dichloromethane at 20℃; for 3 h; Inert atmosphere General procedure: To a solution of triethylamine trihydrofluoride (1equiv.) in dichloromethane (2mL) at room temperature was added the N,N-disubstituted aminodifluorosulfinium tetrafluoroborate (1.5equiv.) followed by 1,4-dioxaspiro[4.5]decan-8-one (1.0mmol, 1equiv.). After 3h of stirring under nitrogen, the reaction mixture was quenched at room temperature with a 5percent aqueous sodium bicarbonate solution, stirred for 15min, and the resulting mixture was extracted twice using dichloromethane. The organic phases were combined, dried over sodium sulfate and solvents were evaporated under low-vacuum at 40°C. NMR yield was calculated by integration of 19F NMR and/or 1H NMR signals of the resulting crude material+internal standard (2-fluoro-4-nitrotoluene).
Reference: [1] Journal of Organic Chemistry, 2010, vol. 75, # 10, p. 3401 - 3411
[2] Organic Letters, 2013, vol. 15, # 5, p. 1088 - 1091
[3] Tetrahedron, 2013, vol. 69, # 20, p. 4066 - 4075
[4] Patent: US2003/149036, 2003, A1,
[5] Journal of Fluorine Chemistry, 2013, vol. 153, p. 57 - 60
[6] Patent: US2006/293392, 2006, A1, . Location in patent: Page/Page column 51
[7] Patent: WO2008/7930, 2008, A1, . Location in patent: Page/Page column 28
[8] Patent: WO2009/48547, 2009, A1, . Location in patent: Page/Page column 40
[9] Patent: US2010/120783, 2010, A1, . Location in patent: Page/Page column 10
[10] Patent: WO2010/56022, 2010, A2, . Location in patent: Page/Page column 23
[11] Patent: EP2786986, 2014, A2, . Location in patent: Paragraph 0122-0124
[12] Patent: CN105985355, 2016, A, . Location in patent: Paragraph 0670; 0671; 0672; 0673
  • 3
  • [ 4746-97-8 ]
  • [ 176251-49-3 ]
  • [ 142273-44-7 ]
YieldReaction ConditionsOperation in experiment
60% With pyrrolidinodifluorosulfiniumtetrafluoroborate; triethylamine tris(hydrogen fluoride) In dichloromethane at 20℃; for 3 h; Inert atmosphere General procedure: To a solution of triethylamine trihydrofluoride (1equiv.) in dichloromethane (2mL) at room temperature was added the N,N-disubstituted aminodifluorosulfinium tetrafluoroborate (1.5equiv.) followed by 1,4-dioxaspiro[4.5]decan-8-one (1.0mmol, 1equiv.). After 3h of stirring under nitrogen, the reaction mixture was quenched at room temperature with a 5percent aqueous sodium bicarbonate solution, stirred for 15min, and the resulting mixture was extracted twice using dichloromethane. The organic phases were combined, dried over sodium sulfate and solvents were evaporated under low-vacuum at 40°C. NMR yield was calculated by integration of 19F NMR and/or 1H NMR signals of the resulting crude material+internal standard (2-fluoro-4-nitrotoluene).
Reference: [1] Journal of Fluorine Chemistry, 2013, vol. 153, p. 57 - 60
[2] Organic Letters, 2009, vol. 11, # 21, p. 5050 - 5053
[3] Journal of Organic Chemistry, 2010, vol. 75, # 10, p. 3401 - 3411
[4] Tetrahedron, 2013, vol. 69, # 20, p. 4066 - 4075
[5] Patent: CN107827721, 2018, A, . Location in patent: Paragraph 0100-0105
  • 4
  • [ 4746-97-8 ]
  • [ 176251-49-3 ]
Reference: [1] Patent: US2014/336378, 2014, A1, . Location in patent: Paragraph 0190; 0191; 0192; 0193
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