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[ CAS No. 68119-31-3 ] {[proInfo.proName]}

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Chemical Structure| 68119-31-3
Chemical Structure| 68119-31-3
Structure of 68119-31-3 * Storage: {[proInfo.prStorage]}
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Product Details of [ 68119-31-3 ]

CAS No. :68119-31-3 MDL No. :MFCD09923942
Formula : C9H5F2NO2 Boiling Point : -
Linear Structure Formula :- InChI Key :OGDSGFSPCQGELG-UHFFFAOYSA-N
M.W :197.14 Pubchem ID :20311384
Synonyms :

Calculated chemistry of [ 68119-31-3 ]

Physicochemical Properties

Num. heavy atoms : 14
Num. arom. heavy atoms : 6
Fraction Csp3 : 0.22
Num. rotatable bonds : 1
Num. H-bond acceptors : 5.0
Num. H-bond donors : 0.0
Molar Refractivity : 42.17
TPSA : 42.25 Ų

Pharmacokinetics

GI absorption : High
BBB permeant : Yes
P-gp substrate : No
CYP1A2 inhibitor : Yes
CYP2C19 inhibitor : No
CYP2C9 inhibitor : No
CYP2D6 inhibitor : No
CYP3A4 inhibitor : No
Log Kp (skin permeation) : -5.83 cm/s

Lipophilicity

Log Po/w (iLOGP) : 1.92
Log Po/w (XLOGP3) : 2.36
Log Po/w (WLOGP) : 2.91
Log Po/w (MLOGP) : 1.14
Log Po/w (SILICOS-IT) : 2.56
Consensus Log Po/w : 2.18

Druglikeness

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

Water Solubility

Log S (ESOL) : -2.8
Solubility : 0.312 mg/ml ; 0.00158 mol/l
Class : Soluble
Log S (Ali) : -2.89
Solubility : 0.255 mg/ml ; 0.0013 mol/l
Class : Soluble
Log S (SILICOS-IT) : -3.19
Solubility : 0.126 mg/ml ; 0.000641 mol/l
Class : Soluble

Medicinal Chemistry

PAINS : 0.0 alert
Brenk : 0.0 alert
Leadlikeness : 1.0
Synthetic accessibility : 2.08

Safety of [ 68119-31-3 ]

Signal Word:Warning Class:N/A
Precautionary Statements:P280-P305+P351+P338 UN#:N/A
Hazard Statements:H302 Packing Group:N/A
GHS Pictogram:

Application In Synthesis of [ 68119-31-3 ]

* 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 [ 68119-31-3 ]
  • Downstream synthetic route of [ 68119-31-3 ]

[ 68119-31-3 ] Synthesis Path-Upstream   1~18

  • 1
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YieldReaction ConditionsOperation in experiment
95% With NaCN In water; dimethyl sulfoxide Synthesis of (2,2-difluoro-1,3-benzodioxol-5-yl)-acetonitrile
A solution of 5-chloromethyl-2,2-difluoro-1,3-benzodioxole (1 eq) in DMSO (1.25 vol) is added to a slurry of NaCN (1.4 eq) in DMSO (3 vol) maintaining the temperature between 30-40° C.
The mixture is stirred for 1 hour then water (6 vol) is added followed by MTBE (4 vol).
After stirring for 30 min, the layers are separated.
The aqueous layer is extracted with MTBE (1.8 vol).
The combined organic layers are washed with water (1.8 vol), dried (Na2SO4), filtered, and concentrated to afford crude (2,2-difluoro-1,3-benzodioxol-5-yl)-acetonitrile (95percent) that is used directly in the next step.
The remaining steps are the same as described above for the synthesis of the acid moiety.
92% With sodium cyanide In dimethyl sulfoxide at 20 - 40℃; for 2 h; Step 4step 4 5[00160] 2-(2.2-difluorobenzordi ri .31dioxol-5-yl)acetonitrile: 5-(chloromethyl)-2,2- difluoro-2H-l,3-benzodioxole (12.36 g, 60 mmol, 1.00 equiv.) was dissolved in DMSO (120 mL). This was followed by the addition of NaCN (4.41 g, 1.50 equiv.) with the inert temperature below 40 °C. The resulting solution was stirred for 2 hours at room temperature. The reaction progress was monitored by GCMS. The reaction was then quenched by the addition of 300 mL of water/ice. The resulting solution was extracted with 3 x 100 mL of ethyl acetate. The organic layers combined and washed with 3 x 100 mL brine dried over anhydrous sodium sulfate and concentrated under vacuum to afford 10.84 g (92percent) of 2-(2,2- difluoro-2H-l ,3-benzodioxol-5-yl)acetonitrile as brown oil.
Reference: [1] Patent: US2012/15999, 2012, A1,
[2] Patent: WO2016/109362, 2016, A1, . Location in patent: Paragraph 00160
[3] Patent: US2011/98311, 2011, A1,
[4] Patent: US2011/98311, 2011, A1,
[5] Patent: US2011/98311, 2011, A1,
[6] Patent: WO2013/185112, 2013, A1, . Location in patent: Paragraph 00561
  • 2
  • [ 1335233-51-6 ]
  • [ 68119-31-3 ]
YieldReaction ConditionsOperation in experiment
68.3% With hydrogenchloride; dimethyl sulfoxide In water at 110℃; for 5 h; To the solution of Example 2D (8 g, 29.7 mmol) in dimethyl sulfoxide (80 mL) was added 3 M aqueous HC1 (80 mL) and the reaction was heated at 110 °C for 5 hours. Two additional vials were set up as described above. After completion of the reaction, all three reaction mixtures were combined. The reaction was extracted with methyl tert-butyl ether (2 x 500 mL) and the combined organics were washed with brine, dried over Na2SO4, filtered and concentrated to give a residue, which was purified by column chromatography on silica gel (petroleum ether/ethyl acetate = 5/1) to provide the title compound (12 g, 68.3 percent yield). ‘H NMR (400 MHz, DMSO-d6) 6 ppm 3.24 - 3.56 (m, 1 H) 4.02 (s, 2 H) 7.20 (d, J=8.38 Hz, 1 H) 7.34 - 7.43 (m, 2 H).
95 %Chromat. With hydrogenchloride In water; dimethyl sulfoxide at 40 - 75℃; The DMSO solution of (2,2-difluoro-1,3-benzodioxol-5-yl)-1-ethylacetate-acetonitrile from above was charged with 3 N HCl (617.3 mL, 1.85 mol) over 20 min while maintaining an internal temperature 99percent was observed (typically after 5-6 h), the reaction was cooled to 20-25° C. and extracted with MTBE (2×525 mL), with sufficient time to allow for complete phase separation during the extractions. The combined organic extracts were washed with 5percent NaCl (2×375 mL). The solution was then transferred to equipment appropriate for a 1.5-2.5 Torr vacuum distillation that was equipped with a cooled receiver flask. The solution was concentrated under vacuum at <60° C. to remove the solvents. (2,2-Difluoro-1,3-benzodioxol-5-yl)-acetonitrile was then distilled from the resulting oil at 125-130° C. (oven temperature) and 1.5-2.0 Ton. (2,2-Difluoro-1,3-benzodioxol-5-yl)-acetonitrile was isolated as a clear oil in 66percent yield from 5-bromo-2,2-difluoro-1,3-benzodioxole (2 steps) and with an HPLC purity of 91.5percent AUC (corresponds to a w/w assay of 95percent). 1H NMR (500 MHz, DMSO) δ 7.44 (br s, 1H), 7.43 (d, J=8.4 Hz, 1H), 7.22 (dd, J=8.2, 1.8 Hz, 1H), 4.07 (s, 2H).
Reference: [1] Patent: WO2018/116185, 2018, A1, . Location in patent: Paragraph 00220
[2] Patent: WO2011/119984, 2011, A1, . Location in patent: Page/Page column 48-49
[3] Patent: US2013/116238, 2013, A1, . Location in patent: Paragraph 0285; 0286
[4] Patent: US2013/186801, 2013, A1, . Location in patent: Paragraph 0359; 0360
[5] Patent: WO2013/185112, 2013, A1, . Location in patent: Paragraph 00563
[6] Patent: WO2014/14841, 2014, A1, . Location in patent: Paragraph 00310; 00311
[7] Patent: WO2014/71122, 2014, A1, . Location in patent: Paragraph 00145; 00146; 00290; 00291
[8] Patent: WO2015/73231, 2015, A1, . Location in patent: Paragraph 00305-00306
[9] Patent: US2016/324788, 2016, A1, . Location in patent: Paragraph 0359; 0360
[10] Patent: WO2018/107100, 2018, A1, . Location in patent: Paragraph 00251
  • 3
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YieldReaction ConditionsOperation in experiment
95% at 30 - 40℃; for 1 h; Synthesis of (2,2-difluoro-l,3-benzodioxol-5-yl)-acetonitrile (compound 20).[00242] A solution of Compound 19 (1 eq) in DMSO (1.25 vol) is added to a slurry of NaCN (1.4 eq) in DMSO (3 vol) maintaining the temperature between 30-40 0C. The mixture is stirred for 1 hour then water (6 vol) is added followed by MTBE (4 vol). After stirring for 30 min, the layers are separated. The aqueous layer is extracted with MTBE (1.8 vol). The combined organic layers are washed with water (1.8 vol), dried (Na2SO4), filtered, and concentrated to afford crude compound 20 (95percent) that is used directly in the next step.
66% at 25℃; for 2 h; [00195] 2-(2,2-difluorobenzo[rf] [l,3]dioxol-5-yl)acetonitrileA mixture of 5-(chloromemyl)-2,2-difluorobenzo[
Reference: [1] Patent: WO2009/76142, 2009, A2, . Location in patent: Page/Page column 50
[2] Patent: WO2007/21982, 2007, A2, . Location in patent: Page/Page column 63; 65
[3] Patent: US2007/244159, 2007, A1, . Location in patent: Page/Page column 79
[4] Patent: US2008/9524, 2008, A1, . Location in patent: Page/Page column 382
[5] Patent: US2009/143381, 2009, A1, . Location in patent: Page/Page column 54
[6] Patent: WO2005/75435, 2005, A1, . Location in patent: Page/Page column 149
[7] Patent: WO2008/141119, 2008, A2, . Location in patent: Page/Page column 69-70
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YieldReaction ConditionsOperation in experiment
100% at 30 - 40℃; for 1 h; A solution of 5-chloromethyl-2,2-difluoro-l,3-benzodioxole (1 eq) in DMSO (1.25 vol) is added to a slurry of NaCN (1.4 eq) in DMSO (3 vol) maintaining the temperature between 30-40 0C. The mixture is stirred for 1 hour then water (6 vol) is added followed by MTBE (4 vol). After stirring for 30 min, the layers are separated. The aqueous layer is extracted with MTBE (1.8 vol). The combined organic layers are washed with water (1.8 vol), dried (Na2SO4), filtered, and concentrated to afford crude (2,2-difluoro-l,3-benzodioxol-5-yl)- acetonitrile (95percent) that is used directly in the next step.
Reference: [1] Patent: WO2009/73757, 2009, A1, . Location in patent: Page/Page column 21
[2] Patent: US2009/253736, 2009, A1, . Location in patent: Page/Page column 22
[3] Patent: US2009/246137, 2009, A1, . Location in patent: Page/Page column 32-33
[4] Patent: WO2010/37066, 2010, A2, . Location in patent: Page/Page column 12; 25-26
[5] Patent: WO2010/53471, 2010, A1, . Location in patent: Page/Page column 46-47
[6] Patent: WO2011/119984, 2011, A1, . Location in patent: Page/Page column 47
[7] Patent: US2013/143918, 2013, A1, . Location in patent: Paragraph 0191; 0192
[8] Patent: US2013/116238, 2013, A1, . Location in patent: Paragraph 0275; 0276
[9] Patent: US2013/186801, 2013, A1, . Location in patent: Paragraph 0355; 0356
[10] Patent: WO2014/14841, 2014, A1, . Location in patent: Paragraph 00323; 00324
[11] Patent: WO2014/71122, 2014, A1, . Location in patent: Paragraph 00143; 00145; 00286; 00287
[12] Patent: WO2015/73231, 2015, A1, . Location in patent: Paragraph 00301-00302
[13] Patent: US2015/231142, 2015, A1, . Location in patent: Paragraph 1115; 1354; 1407; 1517; 1975
[14] Patent: US2016/324788, 2016, A1, . Location in patent: Paragraph 0355; 0356
[15] Patent: WO2018/107100, 2018, A1, . Location in patent: Paragraph 00248; 00250
  • 5
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  • [ 68119-31-3 ]
YieldReaction ConditionsOperation in experiment
95% With NaCN In water; dimethyl sulfoxide Synthesis of (2,2-difluoro-1,3-benzodioxol-5-yl)-acetonitrile
A solution of 5-chloromethyl-2,2-difluoro-1,3-benzodioxole (1 eq) in DMSO (1.25 vol) is added to a slurry of NaCN (1.4 eq) in DMSO (3 vol) maintaining the temperature between 30-40° C.
The mixture is stirred for 1 hour then water (6 vol) is added followed by MTBE (4 vol).
After stirring for 30 min, the layers are separated.
The aqueous layer is extracted with MTBE (1.8 vol).
The combined organic layers are washed with water (1.8 vol), dried (Na2SO4), filtered, and concentrated to afford crude (2,2-difluoro-1,3-benzodioxol-5-yl)-acetonitrile (95percent) that is used directly in the next step.
The remaining steps are the same as described above for the synthesis of the acid moiety.
Amine Moiety
95% With NaCN In water; dimethyl sulfoxide (2,2-Difluoro-1,3-benzodioxol-5-yl)-acetonitrile
A solution of 5-chloromethyl-2,2-difluoro-1,3-benzodioxole (1 eq) in DMSO (1.25 vol) was added to a slurry of NaCN (1.4 eq) in DMSO (3 vol) maintaining the temperature between 30-40° C.
The mixture was stirred for 1 hour then water (6 vol) was added followed by MTBE (4 vol).
After stirring for 30 min, the layers were separated.
The aqueous layer was extracted with MTBE (1.8 vol).
The combined organic layers were washed with water (1.8 vol), dried (Na2SO4), filtered, and concentrated to afford crude (2,2-difluoro-1,3-benzodioxol-5-yl)-acetonitrile (95percent) that was used directly in the next step. 1H NMR (500 MHz, DMSO) δ 7.44 (br s, 1H), 7.43 (d, J=8.4 Hz, 1H), 7.22 (dd, J=8.2, 1.8 Hz, 1H), 4.07 (s, 2H).
95% With NaCN In water; dimethyl sulfoxide (2,2-Difluoro-1,3-benzodioxol-5-yl)-acetonitrile
A solution of 5-chloromethyl-2,2-difluoro-1,3-benzodioxole (1 eq) in DMSO (1.25 vol) was added to a slurry of NaCN (1.4 eq) in DMSO (3 vol), while maintaining the temperature between 30-40° C.
The mixture was stirred for 1 h, and then water (6 vol) was added, followed by methyl tert-butyl ether (MTBE) (4 vol).
After stirring for 30 min, the layers were separated.
The aqueous layer was extracted with MTBE (1.8 vol).
The combined organic layers were washed with water (1.8 vol), dried (Na2SO4), filtered, and concentrated to afford crude (2,2-difluoro-1,3-benzodioxol-5-yl)-acetonitrile (95percent) that was used directly in the next step.
Reference: [1] Patent: US2012/46330, 2012, A1,
[2] Patent: US2011/98311, 2011, A1,
[3] Patent: US2011/98311, 2011, A1,
[4] Patent: US9241934, 2016, B2,
  • 6
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YieldReaction ConditionsOperation in experiment
55% at 20℃; for 3 h; General procedure: To a solution of 2, 2-difluorobenzo [1, 3] dioxol-5-yl-methanol (930 mg, 5 mmol) in anhydrous THF (5 ml) was added NaBH4 (208 mg, 5.5 mmol) in portions at T = 0 °C in ten minutes. The mixture was then stirred at the same temperature for about 2 h (controlled with HPLC). H2O (1.5 ml) was added and the mixture was stirred for about 15 min. The mixture was then extracted with diethyl ether (3 * 3 ml) and washed with water (2 * 1 ml). The organic phase was completely dried and lyophilized to obtain 2,2-difluorobenzo [1, 3] dioxol-5-yl-methanol as colorless oil and used without further purification (865 mg, 85percent). A solution of 2,2-difluorobenzo [1, 3] dioxol-5-yl-methanol (865mg, 4.6mmol) in thionyl chloride (2ml) was stirred at room temperature upon completeness. When the reaction was complete (about 1h), the solution was concentrated under vacuum to remove the excess of thionyl chloride. Then, the residue was resuspended in a solution of dichloromethane and saturated NaHCO3 1:1 (2ml). The aqueous layer was then back-extracted with dichloromethane (2×1ml) and the combined organic layers were dried over Na2SO4 and finally concentrated to vacuum to give 5(chloromethyl)-2,2-difluorobenzo [1, 3] dioxole (823mg, 87percent) which was used directly in the next step. A mixture of 5(chloromethyl)-2,2-difluorobenzo [1, 3] dioxole (823 mg, 3.99 mmol) and KCN (519 mg, 7.98 mmol) was stirred in dimethyl sulfoxide (DMSO) (3 ml) for 3 h at room temperature. H2O (1.5 ml) was added and the mixture extracted with ethyl acetate (EtOAc) (3 * 3 ml) and the organic phases were dried over Na2SO4 and concentrated under reduced pressure. The product was purified by preparative HPLC to afford 2(2, 2-difluorbenzo [1, 3] dioxol-5-yl)-acetonitrile (432 mg, 55percent).
Reference: [1] European Journal of Medicinal Chemistry, 2018, vol. 144, p. 179 - 200
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Reference: [1] Patent: US2009/221597, 2009, A1, . Location in patent: Page/Page column 30
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  • [ 68119-31-3 ]
Reference: [1] Patent: WO2011/119984, 2011, A1,
[2] Patent: US2011/98311, 2011, A1,
[3] Patent: US2011/98311, 2011, A1,
[4] Patent: US2011/98311, 2011, A1,
[5] Patent: US2011/98311, 2011, A1,
[6] Patent: US2013/143918, 2013, A1,
[7] Patent: US2013/186801, 2013, A1,
[8] Patent: WO2013/185112, 2013, A1,
[9] Patent: WO2014/14841, 2014, A1,
[10] Patent: WO2014/71122, 2014, A1,
[11] Patent: WO2015/73231, 2015, A1,
[12] Patent: US2015/231142, 2015, A1,
[13] Patent: WO2016/109362, 2016, A1,
[14] Patent: US2016/324788, 2016, A1,
[15] Patent: WO2018/116185, 2018, A1,
[16] Patent: US2013/116238, 2013, A1,
[17] Patent: WO2008/141119, 2008, A2,
  • 9
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  • [ 68119-31-3 ]
Reference: [1] Patent: WO2011/119984, 2011, A1,
[2] Patent: US2012/15999, 2012, A1,
[3] Patent: US2012/46330, 2012, A1,
[4] Patent: US2011/98311, 2011, A1,
[5] Patent: US2011/98311, 2011, A1,
[6] Patent: US2011/98311, 2011, A1,
[7] Patent: US2011/98311, 2011, A1,
[8] Patent: US2013/143918, 2013, A1,
[9] Patent: US2013/186801, 2013, A1,
[10] Patent: US2016/324788, 2016, A1,
[11] Patent: WO2013/185112, 2013, A1,
[12] Patent: WO2014/14841, 2014, A1,
[13] Patent: WO2014/71122, 2014, A1,
[14] Patent: WO2015/73231, 2015, A1,
[15] Patent: US2015/231142, 2015, A1,
[16] Patent: US9241934, 2016, B2,
[17] Patent: US2011/98311, 2011, A1,
[18] Patent: US2011/98311, 2011, A1,
[19] Patent: US2011/98311, 2011, A1,
[20] Patent: US2011/98311, 2011, A1,
[21] Patent: US2013/116238, 2013, A1,
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  • [ 68119-31-3 ]
Reference: [1] Patent: WO2011/119984, 2011, A1,
[2] Patent: US2012/15999, 2012, A1,
[3] Patent: US2012/46330, 2012, A1,
[4] Patent: US2011/98311, 2011, A1,
[5] Patent: US2011/98311, 2011, A1,
[6] Patent: US2011/98311, 2011, A1,
[7] Patent: US2011/98311, 2011, A1,
[8] Patent: US2013/143918, 2013, A1,
[9] Patent: US2013/116238, 2013, A1,
[10] Patent: US2013/186801, 2013, A1,
[11] Patent: US2016/324788, 2016, A1,
[12] Patent: WO2013/185112, 2013, A1,
[13] Patent: WO2014/14841, 2014, A1,
[14] Patent: WO2014/71122, 2014, A1,
[15] Patent: WO2015/73231, 2015, A1,
[16] Patent: US2015/231142, 2015, A1,
[17] Patent: US9241934, 2016, B2,
[18] Patent: WO2016/109362, 2016, A1,
[19] European Journal of Medicinal Chemistry, 2018, vol. 144, p. 179 - 200
[20] Patent: WO2018/107100, 2018, A1,
[21] Patent: WO2008/141119, 2008, A2,
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  • [ 68119-31-3 ]
Reference: [1] Patent: US2011/98311, 2011, A1,
[2] Patent: US2011/98311, 2011, A1,
[3] Patent: US2011/98311, 2011, A1,
[4] Patent: US2011/98311, 2011, A1,
[5] Patent: US2015/231142, 2015, A1,
[6] Patent: WO2016/109362, 2016, A1,
[7] Patent: WO2008/141119, 2008, A2,
  • 12
  • [ 7145-99-5 ]
  • [ 68119-31-3 ]
Reference: [1] Patent: US4105780, 1978, A,
  • 13
  • [ 68119-28-8 ]
  • [ 68119-31-3 ]
Reference: [1] Patent: US4105780, 1978, A,
  • 14
  • [ 68119-31-3 ]
  • [ 107-04-0 ]
  • [ 862574-87-6 ]
YieldReaction ConditionsOperation in experiment
100% With tetraoctyl ammonium bromide; potassium hydroxide In water at 70℃; for 1 h; A mixture of (2,2-difluoro-l,3-benzodioxol-5-yl)-acetonitrile (1.0 eq), 50 wt percent aqueous KOH (5.0 eq) l-bromo-2-chloroethane (1.5 eq), and OCt4NBr (0.02 eq) is heated at 70 0C for 1 h. The reaction mixture is cooled then worked up with MTBE and water. The organic phase is washed with water and brine then the solvent is removed to afford (2,2-difluoro-l,3- benzodioxol-5-yl)-cyclopropanecarbonitrile.
100% With potassium hydroxide In water at 70℃; for 1 h; A mixture of (2,2-difluoro-l,3-benzodioxol-5-yl)-acetonitrile (1.0 eq), 50 wt percent aqueous KOH (5.0 eq) l-bromo-2-chloroethane (1.5 eq), and OCt4NBr (0.02 eq) is heated at 70 0C for 1 h. The reaction mixture is cooled then worked up with MTBE and water. The organic phase is washed with water and brine then the solvent is removed to afford (2,2-difluoro-l,3-benzodioxol-5-yl)-cyclopropanecarbonitrile.
100% With tetraoctyl ammonium bromide; potassium hydroxide In water at 70℃; for 1 h; Preparation of (2,2-difluoro-1,3-benzodioxol-5-yl)-cyclopropanecarbonitrile
A mixture of (2,2-difluoro-1,3-benzodioxol-5-yl)-acetonitrile (1.0 eq), 50 wt percent aqueous KOH (5.0 eq) 1-bromo-2-chloroethane (1.5 eq), and Oct4NBr (0.02 eq) was heated at 70° C. for 1 h.
The reaction mixture was cooled, then worked up with MTBE and water.
The organic phase was washed with water and brine.
The solvent was removed to afford (2,2-difluoro-1,3-benzodioxol-5-yl)-cyclopropanecarbonitrile.
88% With potassium hydroxide; tetraoctyl ammonium bromide In water at 70℃; for 1 h; Synthesis of ^^-difluoro-l^-benzodioxol-S-y^-cyclopropanecarbonitrile (compound 21). l-bromo-2-chloroethane (1.5 equiv) 50percent KOH (5.0 equiv) OCt4NBr (0.02 equiv) 70 degrees C 88- 100percent yield [00244] A mixture of compound 20 (1.0 eq), 50 wt percent aqueous KOH (5.0 eq) l-bromo-2- chloroethane (1.5 eq), and OCt4NBr (0.02 eq) is heated at 70 0C for 1 h. The reaction mixture is cooled then worked up with MTBE and water. The organic phase is washed with water and brine then the solvent is removed to afford compound 21.
10.12 g With tetrabutylammomium bromide; sodium hydroxide In ethanol; water at 70℃; for 48 h; Inert atmosphere Step 5[00161] l -(2.2-difluoro-2H-1.3-benzodioxol-5-yl)cvclopropane-l -carbonitrile: To a 100 mL round-bottom flask purged and maintained with an inert atmosphere of nitrogen, were placed 2-(2,2-difluoro-2H-l ,3-benzodioxol-5-yl)acetonitrile (10.84 g, 55 mmol, 1.00 equiv.),NaOH (50percent) in water), 1 -bromo-2-chloroethane (11.92g, 82.5 mmol, 1.50 equiv.), BmNBr(361 mg, 1.1 mmol, 0.02 equiv.). The resulting solution was stirred for 48 h at 70 °C. The reaction progress was monitored by GCMS. The reaction mixture was cooled. The resulting solution was extracted with 3 x 200 mL of ethyl acetate and the organic layers combined. The resulting mixture was washed with 1 x 200 mL of brine. The mixture was dried over anhydrous sodium sulfate and concentrated under vacuum to afford 10.12g of 1 -(2,2- difluoro-2H-l,3-benzodioxol-5-yl)cyclopropane-l-carbonitrile as brown oil.

Reference: [1] Patent: WO2009/73757, 2009, A1, . Location in patent: Page/Page column 21
[2] Patent: WO2010/37066, 2010, A2, . Location in patent: Page/Page column 12; 26
[3] Patent: US2016/324788, 2016, A1, . Location in patent: Paragraph 0361; 0362
[4] Patent: WO2009/76142, 2009, A2, . Location in patent: Page/Page column 51
[5] Patent: US2007/244159, 2007, A1, . Location in patent: Page/Page column 79
[6] Patent: US2008/9524, 2008, A1, . Location in patent: Page/Page column 381
[7] Patent: US2009/143381, 2009, A1, . Location in patent: Page/Page column 54
[8] Patent: US2009/221597, 2009, A1, . Location in patent: Page/Page column 30
[9] Patent: US2009/253736, 2009, A1, . Location in patent: Page/Page column 22-23
[10] Patent: US2009/246137, 2009, A1, . Location in patent: Page/Page column 32-33
[11] Patent: WO2005/75435, 2005, A1, . Location in patent: Page/Page column 149
[12] Patent: WO2010/53471, 2010, A1, . Location in patent: Page/Page column 46-48
[13] Patent: WO2011/119984, 2011, A1, . Location in patent: Page/Page column 49
[14] Patent: US2013/143918, 2013, A1, . Location in patent: Paragraph 0197; 0198
[15] Patent: US2013/116238, 2013, A1, . Location in patent: Paragraph 0277; 0278
[16] Patent: US2013/186801, 2013, A1, . Location in patent: Paragraph 0361; 0362
[17] Patent: WO2013/185112, 2013, A1, . Location in patent: Paragraph 00564
[18] Patent: WO2014/14841, 2014, A1, . Location in patent: Paragraph 00312; 00313
[19] Patent: WO2014/71122, 2014, A1, . Location in patent: Paragraph 00143; 00145; 00292; 00293
[20] Patent: WO2015/73231, 2015, A1, . Location in patent: Paragraph 00307-00308
[21] Patent: US2015/231142, 2015, A1, . Location in patent: Paragraph 1116; 1355; 1518; 1519; 1976
[22] Patent: WO2016/109362, 2016, A1, . Location in patent: Paragraph 00161
[23] Patent: WO2018/107100, 2018, A1, . Location in patent: Paragraph 00248; 00250; 00251
[24] Patent: WO2008/141119, 2008, A2, . Location in patent: Page/Page column 69-70
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YieldReaction ConditionsOperation in experiment
85% With 1,8-diazabicyclo[5.4.0]undec-7-ene In dimethyl sulfoxide at 21℃; for 12 h; General procedure: To a 5 mL Schlenk tube were added aryl / heteroaryl acetonitriles 1 (1.0 mmol, 1.0 equiv.), vinyl diphenylsulfonium triflate (434.4 mg, 1.2 mmol, 1.2 equiv.), and DMSO (5 mL). The mixture was stirred at room temperature for 2 min and to the mixture DBU (456 mg, 3 mmol, 3.0 equiv.) was added. The mixture was stirred for 12 hours at room temperature, and then to the mixture was added saturated ammonium chloride solution (25 mL). The resulting mixture was extracted with EtOAc (3 x 150 mL). The combined organic layers were washed with H2O (2 x 30 mL), dried with anhydrous sodium sulfate. After concentration, product 2 was purified using silica gel column chromatography using an appropriate eluent.
Reference: [1] Tetrahedron Letters, 2018, vol. 59, # 14, p. 1443 - 1445
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Reference: [1] Patent: US2011/98311, 2011, A1,
[2] Patent: US2011/98311, 2011, A1,
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Reference: [1] Patent: US9241934, 2016, B2,
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  • [ 1152311-62-0 ]
Reference: [1] Patent: WO2011/119984, 2011, A1,
[2] Patent: US2013/143918, 2013, A1,
[3] Patent: WO2013/185112, 2013, A1,
[4] Patent: WO2014/14841, 2014, A1,
[5] Patent: US2015/231142, 2015, A1,
[6] Patent: WO2018/107100, 2018, A1,
[7] Patent: US2013/116238, 2013, A1,
[8] Patent: WO2019/18395, 2019, A1,
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