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Chemical Structure| 68432-92-8
Chemical Structure| 68432-92-8
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Product Details of [ 68432-92-8 ]

CAS No. :68432-92-8 MDL No. :MFCD07783720
Formula : C10H9NO2 Boiling Point : -
Linear Structure Formula :- InChI Key :XSNUGLQVCGENEM-UHFFFAOYSA-N
M.W : 175.18 Pubchem ID :10821136
Synonyms :

Calculated chemistry of [ 68432-92-8 ]      Expand+

Physicochemical Properties

Num. heavy atoms : 13
Num. arom. heavy atoms : 6
Fraction Csp3 : 0.2
Num. rotatable bonds : 3
Num. H-bond acceptors : 3.0
Num. H-bond donors : 0.0
Molar Refractivity : 47.24
TPSA : 50.09 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) : -5.91 cm/s

Lipophilicity

Log Po/w (iLOGP) : 1.91
Log Po/w (XLOGP3) : 2.06
Log Po/w (WLOGP) : 1.54
Log Po/w (MLOGP) : 1.59
Log Po/w (SILICOS-IT) : 2.03
Consensus Log Po/w : 1.83

Druglikeness

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

Water Solubility

Log S (ESOL) : -2.37
Solubility : 0.752 mg/ml ; 0.00429 mol/l
Class : Soluble
Log S (Ali) : -2.74
Solubility : 0.318 mg/ml ; 0.00182 mol/l
Class : Soluble
Log S (SILICOS-IT) : -2.96
Solubility : 0.192 mg/ml ; 0.00109 mol/l
Class : Soluble

Medicinal Chemistry

PAINS : 0.0 alert
Brenk : 0.0 alert
Leadlikeness : 1.0
Synthetic accessibility : 1.5

Safety of [ 68432-92-8 ]

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 [ 68432-92-8 ]

* 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 [ 68432-92-8 ]
  • Downstream synthetic route of [ 68432-92-8 ]

[ 68432-92-8 ] Synthesis Path-Upstream   1~16

  • 1
  • [ 68432-92-8 ]
  • [ 5689-33-8 ]
YieldReaction ConditionsOperation in experiment
79% With lithium hydroxide; water In tetrahydrofuran at 20 - 50℃; Lithium hydroxide (493 mg, 11.7 mmol) was added to a stirred solution of methyl 3- (cyanomethyl) benzoate (1.029 g, 5.87 mmol) in THF (10 ml) and water (0.5 ml) at ambient temperature. The reaction mixture was stirred at 50 °C overnight. The solvent was evaporated and the residue partitioned between water and diethyl ether. The water phase was extracted 3 times with diethyl ether. The aqueous phase was acidified with conc. HC1 and was extracted an additional 3 times with diethyl ether. The collected organic phases were dried (NA2S04) and concentrated IN VACUO, giving 745 mg (79percent) of the title compound. 1H NMR (DMSO-D6) : 8 13.11 (1H, s), 7.95 (1H, s), 7.90 (1H, d, J=7.6 HZ), 7.60 (1H, M), 7.53 (1H, t, J=7.6 Hz), 4.14 (2H, s); MS (ESI) m/z 160 (M-1).
Reference: [1] Patent: WO2004/96781, 2004, A1, . Location in patent: Page 80
  • 2
  • [ 1129-28-8 ]
  • [ 68432-92-8 ]
YieldReaction ConditionsOperation in experiment
91% With 18-crown-6 ether In acetonitrile at 20℃; for 72 h; (i) Production of methyl 3-(cyanomethyl)benzoate; To a solution of methyl 3-bromobenzoate (10.0 g, 44 mmol) in acetonitrile (100 mL) were added potassium cyanide (5.7 g, 87 mmol) and 18-crown-6 (1.0 g), and the mixture was stirred at room temperature for 3 days. The reaction mixture was filtered, and the solvent was evaporated under reduced pressure. The residue was purified by silica gel column chromatography (ethyl acetate/hexane=5/95-->30/70), and the fraction containing the object product was concentrated under reduced pressure to give the title compound (7.0 g, 91percent) as a colorless oil. 1H-NMR (DMSO-d6, 300 MHz) δ 3.88 (3H, s), 4.17 (2H, s), 7.57 (1H, t, J = 7.6 Hz), 7.61 - 7.69 (1H, m), 7.88 - 7.95 (1H, m), 7.97 (1H, br s).
Reference: [1] Patent: EP2181987, 2010, A1, . Location in patent: Page/Page column 65; 110; 115
[2] Journal of Medicinal Chemistry, 2012, vol. 55, # 7, p. 3452 - 3478
[3] Angewandte Chemie - International Edition, 2010, vol. 49, # 37, p. 6633 - 6637
[4] Chemistry - A European Journal, 2012, vol. 18, # 5, p. 1383 - 1400
[5] Patent: WO2008/156820, 2008, A1, . Location in patent: Page/Page column 59
[6] Patent: WO2016/165014, 2016, A1, . Location in patent: Page/Page column 22
  • 3
  • [ 143-33-9 ]
  • [ 1129-28-8 ]
  • [ 68432-92-8 ]
YieldReaction ConditionsOperation in experiment
70% at 75℃; for 5 h; A suspension of methyl-3-(bromomethyl)benzoate (13.5 g, 58.9 mmol) arid sodium cyanide (4.33 g, 88.4 mmol) in DMf (25 ml) and water (1 ml) was stirred at 75 °C for 5 h. The reaction mixture was quenched with water (50 ml) and extracted with EtOAc (100 ml x 3). The combined orgaiiics were dried and concentrated under reduced pressure. The resulting residue was purified by column chromatography utilizing an ISCO system (hexane-EtOAc) to give 7.2 g (70percent) of colourless oil. NMR: 7.90 (s, I H), 7.86 (d, IH), 7.60 (d, IH), 7.50 (m, IH), 4.10 (s, 2H), 3.80 (s, 3H); m/z 175.
70% at 75℃; for 5 h; Method 1; 3-Cγanomethyl-benzoic acid methyl esterA suspension of methyl-3-(bromomethyl)benzoate (13.5 g, 58.9 mmol) and sodium cyanide (4.33 g5 88.4 mmol) in DMF (25 ml) and water (1 ml) was stirred at 75 °C for 5 h. The reaction mixture was quenched with water (50 ml) and extracted with EtOAc (100 ml x 3). The combined organics were dried (Na2SO4) and concentrated under reduced pressure. The resulting residue was purified by column chromatography utilizing an ISCO system (hexane-EtOAc) to give 7.2 g (70percent) of colourless oil. NMR: 7.90 (s5 IH), 7.86 (d, IH), 7.60 (d, IH)5 7.50 (m5 IH)5 4.10 (s, 2H)5 3.80 (s, 3H); m/z 175.
70%
Stage #1: at 75℃; for 5 h;
Stage #2: With water In N,N-dimethyl-formamide
A suspension of methyl-3-(bromomethyl)benzoate (13.5 g, 58.9 mmol) and sodium cyanide (4.33 g, 88.4 mmol) in DMF (25 ml) and water (1 ml) was stirred at 75 °C for 5 h. The reaction mixture was quenched with water (50 ml) and extracted with EtOAc (3 χ 100 ml). The combined organics were dried and concentrated under reduced pressure. The resulting residue was purified by column chromatography utilizing an ISCO system (hexane- EtOAc) to give7.2 g (70percent) of colourless oil. NMR: 7.90 (s, IH), 7.86 (d, IH), 7.60 (d, IH), 7.50 (m, IH), 4.10 (s, 2H), 3.80 (s, 3H); m/z 175.
70% at 75℃; for 5 h; A suspension of methyl-3-(bromomethyl)benzoate (13.5 g, 58.9 mmol) and sodium cyanide (4.33 g, 88.4 mmol) in DMF (25 ml) and water (1 ml) was stirred at 75 °C for 5 hours. The reaction mixture was quenched with water (50 ml) and extracted with EtOAc (100 ml x 3). The combined organics were dried with Na2SC>4(s) and concentrated under reduced pressure. The resulting residue was purified by column chromatography utilizing an ISCO system (hexane-EtOAc) to give7.2 g (70percent) of colourless oil. NMR (400 MHz): 7.90 (s, 1H), 7.86 (d, 1H), 7.60 (d, 1H), 7.50 (m, 1H), 4.10 (s, 2H), 3.80 (s, 3H); m/z 175.
70% at 75℃; for 5 h; Method 15; 3-Cvanomethyl-benzoic acid methyl ester; A suspension of methyl-3-(bromomethyl)benzoate (13.5 g, 58.9 mmol) and sodium cyanide (4.33 g, 88.4 mmol) in DMF (25 ml) and water (1 ml) was stirred at 75 °C for 5 hours. The reaction mixture was quenched with water (50 ml), extracted with EtOAc (3 x 100 <n="52"/>ml) and the combined organics were dried and concentrated under reduced pressure. The residue was purified by column chromatography utilizing an ISCO system (hexane-EtOAc) to give 7.2 g (70percent) of a colourless oil.1HNMR: 7.90 (s, IH), 7.86 (d, IH), 7.60 (d, IH), 7.50 (m, IH), 4.10 (s, 2H), 3.80 (s, 3H); m/z: 175.
70% at 75℃; for 5 h; Method 9; 3-Cvanomethyl-benzoic acid methyl ester; A suspension of niethyl-3-(bromomethyl)benzoate (13.5 g, 58.9 mmol) and sodium cyanide (4.33 g, 88.4 mmol) in DMF (25 ml) and water (1 ml) was stirred at 75 °C for 5 h. The reaction mixture was quenched with water and extracted with EtOAc. The combined organics were dried and concentrated under reduced pressure. The resulting residue was purified by column chromatography utilizing an ISCO system (hexane-EtOAc) to give 7.2 g (70percent) of colourless oil. NMR: 7.90 (s, IH), 7.86 (d, IH), 7.60 (d, IH), 7.50 (m, IH), 4.10 (s, 2H), 3.80 (s, 3H); m/z 175.
70% at 75℃; for 5 h; Method 2
3-Cyanomethyl-benzoic acid methyl ester
A suspension of methyl-3-(bromomethyl)benzoate (13.5 g, 58.9 mmol) and sodium cyanide (4.33 g, 88.4 mmol) in DMF (25 ml) and water (1 ml) was stirred at 75 ° C. for 5 h.
The reaction mixture was quenched with water and extracted with EtOAc.
The combined organics were dried with NaCl(sat) and then Na2SO4(s).
The solvents were removed under reduced pressure.
The resulting residue was purified by column chromatography utilizing an 20 ISCO system (hexane-EtOAc) to give 7.2 g (70percent/o) of colourless oil. NMR: 7.90 (s, 1H); 7.86 (d, 1H); 7.60 (d, 1H); 7.50 (m, 1H); 4.10 (s, 2H); 3.80 (s, 3H); m/z 175.
70% at 75℃; for 5 h; Method 50; 3-Cyanomethylbenzoic acid methyl ester; A suspension of methyl-3-(bromomethyl)benzoate (13.5 g, 58.9 mmol) and sodiumcyanide (4.33 g, 88.4 mmol) in DMF (25 ml) and water (1 ml) was stirred at 75 °C for 5hours. The reaction mixture was quenched with water (50 ml) and extracted with EtOAc (100ml x 3). The combined organics were dried with Na2SO4(s) and concentrated under reducedpressure. The resulting residue was purified by column chromatography utilizing an ISCOsystem (hexane-EtOAc) to give7.2 g (70percent) of colourless.oil. NMR (400 MHz): 7.90 (s, 1 H),7.86 (d, 1 H), 7.60 (d, 1 H), 7.50 (m, 1 H)3 4.10 (s, 2 H), 3.80 (s, 3 H); m/z 175.
70% at 75℃; for 5 h; Method 12; 3-Cvanomethyl-benzoic acid methyl ester; A suspension of methyl-3-(bromomethyl)benzoate (13.5 g, 58.9 mmol) and sodium cyanide (4.33 g, 88.4 mmol) in DMF (25 ml) and water (1 ml) was stirred at 75 0C for 5 hours. The reaction mixture was quenched with water (50 ml) and extracted with EtOAc. The combined organics were dried and concentrated under reduced pressure. The resulting residue was purified by column chromatography utilizing an ISCO system (hexane-EtOAc) to give 7.2 g (70percent) of colourless oil. NMR: 7.90 (s, 1Η), 7.86 (d, 1Η), 7.60 (d, 1Η), 7.50 (m, 1Η), 4.10 (s, 2Η), 3.80 (s, 3H); m/z 175.
70% at 75℃; for 5 h; Method 6; 3-Cyanomethyl-benzoic acid methyl ester; A suspension of methyl-3-(bromomethyl)benzoate (13.5 g, 58.9 mmol) and sodium cyanide (4.33 g, 88.4 mmol) in DMF (25 ml) and water (1 ml) was stirred at 75 0C for 5 h. The reaction mixture was quenched with water and extracted with EtOAc. The combined <n="28"/>organics were dried with NaCl(sat) and then Na2S O4(s). The solvents were removed under reduced pressure. The resulting residue was purified by column chromatography utilizing an ISCO system (hexane-EtOAc) to give 7.2 g (70percent) of colourless oil. NMR: 7.90 (s, IH), 7.86 (d, IH), 7.60 (d, IH), 7.50 (m, IH), 4.10 (s, 2H), 3.80 (s, 3H); m/z 175.
70% at 75℃; for 5 h; Method 4; 3-Cyanomethyl-benzoic acid methyl ester; A suspension of methyl-3-(bromomethyl)benzoate (13.5 g, 58.9 mmol) and sodium cyanide (4.33 g, 88.4 mmol) in DMF (25 ml) and water (1 ml) was stirred at 75 °C for 5 hours. The reaction mixture was quenched with water (50 ml) and extracted with EtOAc (3 x 100 ml). The combined organics were dried with Na2S04(s) and concentrated under reduced pressure. The resulting residue was purified by column chromatography utilizing an ISCO system (hexane-EtOAc) to give 7.2 g (70percent) of a colourless oil.

Reference: [1] Patent: WO2006/67446, 2006, A1, . Location in patent: Page/Page column 126
[2] Patent: WO2006/79791, 2006, A1, . Location in patent: Page/Page column 34
[3] Patent: WO2006/24834, 2006, A1, . Location in patent: Page/Page column 63-64
[4] Patent: WO2006/24836, 2006, A1, . Location in patent: Page/Page column 27
[5] Patent: WO2007/71955, 2007, A1, . Location in patent: Page/Page column 50-51
[6] Patent: WO2007/71963, 2007, A2, . Location in patent: Page/Page column 47
[7] Patent: US2009/170849, 2009, A1, . Location in patent: Page/Page column 11
[8] Patent: WO2006/3378, 2006, A1, . Location in patent: Page/Page column 64
[9] Patent: WO2006/40568, 2006, A1, . Location in patent: Page/Page column 62
[10] Patent: WO2007/113557, 2007, A1, . Location in patent: Page/Page column 26-27
[11] Patent: WO2005/123696, 2005, A1, . Location in patent: Page/Page column 66
[12] Journal of Medicinal Chemistry, 2003, vol. 46, # 3, p. 345 - 348
[13] Patent: WO2008/97341, 2008, A2, . Location in patent: Page/Page column 46-47
[14] Bioorganic and Medicinal Chemistry Letters, 2009, vol. 19, # 3, p. 1026 - 1029
  • 4
  • [ 773837-37-9 ]
  • [ 1129-28-8 ]
  • [ 68432-92-8 ]
YieldReaction ConditionsOperation in experiment
89% at 20℃; Step 1: synthesis of methyl 3-(cyanomethyl)benzoate (1)To a solution of 3-(bromomethyl)benzoic acid methyl ester (25 g, 109 mmol) in DMF (250 mL) was added NaCN (5.4 g, 109 mmol). The reaction mixture was stirred overnight at rt. The mixture was poured into water (1.5 L), followed by the extraction with TBME (2 x 500mL). The combined organic layers were washed with water, brine, dried (Na2S04), filtered and evaporated under reduced pressure to yield methyl 3- (cyanomethyl)benzoate 1 (17g, 89percent). 1H-NMR (400 MHz, CDC13) 3.82 (s, 2H), 3.94 (s, 3H), 7.48 (m, 1H), 7.57 (m, 1H), 8.03 (m, 2H).
89% at 20℃; Step 1:
synthesis of methyl 3-(cyanomethyl)benzoate (1)
To a solution of 3-(bromomethyl)benzoic acid methyl ester (25 g, 109 mmol) in DMF (250 mL) was added NaCN (5.4 g, 109 mmol).
The reaction mixture was stirred overnight at rt.
The mixture was poured into water (1.5 L), followed by the extraction with TBME (2*500 mL).
The combined organic layers were washed with water, brine, dried (Na2SO4), filtered and evaporated under reduced pressure to yield methyl 3-(cyanomethyl)benzoate 1 (17 g, 89percent).
1H-NMR (400 MHz, CDCl3) 3.82 (s, 2H), 3.94 (s, 3H), 7.48 (m, 1H), 7.57 (m, 1H), 8.03 (m, 2H).
85% at 75℃; for 5 h; Inert atmosphere A suspension of methyl-3-(bromomethyl)benzoate (0.5 g, 2.18 mmol) and sodium cyanide (0.16 g, 3.27 mmol) in DMF (0.93 mL) and H2O (0.04 mL) was stirred at 75 °C for 5 h. The reaction was quenched with water and extracted with EtOAc. The combined organic layers were washed with H2O (3×), dried (Na2SO4) and the solvents were evaporated. The residue was purified by column chromatography (silica gel, from 80:20 hexane/EtOAc to 70:30 hexane/EtOAc) to afford 0.324 g (85percent) of a colourless oil identified as methyl 3-(cyanomethyl)benzoate 29b. 1H NMR (400.13 MHz, CDCl3): δ 8.02–8.00 (m, 2H, ArH), 7.56–7.53 (m, 1H, ArH), 7.50–7.46 (m, 1H, ArH), 3.93 (s, 3H, CH3), 3.81 (s, 2H, CH2) ppm. 13C NMR (100.62 MHz, CDCl3): δ 166.3 (s), 132.3 (d), 131.0 (s), 130.5 (s), 129.3 (d), 129.2 (d), 129.1 (d), 117.5 (s), 52.3 (q), 23.4 (t) ppm. HMRS (ESI+): Calcd for C10H10NO2 ([M+H]+), 176.0706; found, 176.0703. IR (NaCl): ν 3003 (w, C–H), 2954 (w, C–H), 2252 (w, CN), 1722 (s, CO), 1439 (m), 1287 (m) cm−1. UV (MeOH): λmax 283, 229 nm.
81% at 65℃; for 2 h; Methyl 3-(cyanomethyl)benzoate 15. To a stirring aqueous solution (60 mL) of potassium cyanide (3.62 g, 55.7 mmol) at 65°C was added dropwise methyl 3-(bromomethyl)benzoate 14 (10.2 g, 44.5 mmol) in absolute ethanol (50 mL) over a period of 0.5 h. After addition, the reaction was stirred for 1.5 h at 65°C. The solution was then diluted with absolute ethanol (500 mL), cooled on ice bath, filtered, and concentrated with a rotary evaporator. The crude was treated with chloroform (350 mL), dried over MgS04, filtered, concentrated, and used without further purification. Yield 6.3 g (81percent). 3/4-NMR (CDC13): 3.81 br s (2H, CH2), 3.93 s (3H, CH3); 7.45-7.51 m (1H, CH), 7.53-7.58 m (1H, CH), 7.99-8.04 m (2H, CH).
51% at 0 - 10℃; for 3.25 h; To a cold solution of Intermediate BM (7.2 g, 31.44 mmol) in DMSO (35.0 mL) at 0 °C was added a sodium cyanide (3.0 g, 62.88 mmol) portionwise over 15 minutes. After the addition was complete, the reaction mixture was allowed to stir at 10 °C for 3 hours. Ice cold water was added to the reaction mixture (50 mL), and the reaction was extracted with ethyl acetate (3 χ 50 mL), washed with water (2 χ 25 mL) and brine (25 mL), dried over anhydrous Na2S04, and the solvent was removed to afford the crude product. This material was purified by column chromatography (silica gel 100-200 mesh) using 10percent ethyl acetate in petroleum ether as the eluent to afford Intermediate BN (2.8 g, 51percent) as a pale brown liquid. NMR (CDC13): δ 9.44-9.42 (m, 2H), 8.90-8.78 (m, 2H), 4.63 (s, 3H), 4.49 (s, 2H). Mass (M-H): 174.1.

Reference: [1] Patent: WO2011/147764, 2011, A1, . Location in patent: Page/Page column 25
[2] Patent: US2013/79341, 2013, A1, . Location in patent: Paragraph 0104
[3] Bioorganic and Medicinal Chemistry, 2013, vol. 21, # 7, p. 2056 - 2067
[4] Patent: WO2012/173784, 2012, A1, . Location in patent: Page/Page column 28-29
[5] Journal of Organic Chemistry, 2017, vol. 82, # 2, p. 1114 - 1126
[6] Patent: WO2011/47156, 2011, A1, . Location in patent: Page/Page column 89
[7] Patent: US2009/275583, 2009, A1, . Location in patent: Page/Page column 30
  • 5
  • [ 151-50-8 ]
  • [ 1129-28-8 ]
  • [ 68432-92-8 ]
YieldReaction ConditionsOperation in experiment
96% With 18-crown-6 ether In acetonitrile for 24 h; Heating / reflux To methyl 3-bromomethyl-benzoate (25.28 g, 0.11 mol) in acetonitrile (230 ml) is added potassiumcyanide (14.3 g, 0.22 mmol) and 18-crown-6 (1.00 g, 2.6 mmol) and the mixture is heated to reflux for24 h. After filtration, the crude product is transferred to the next step without any further purification.Yield: 18.5 g (96 percent)
68% at 60℃; a) methyl 3-(cyanomethyl)benzoateA slurry of methyl 3-(bromomethyl)benzoate (4.0 g, 17.5 mmol) and potassium cyanide (1.2 g, 18.4 mmol) in ethanol (40 ml) was heated at 60 °C over night, filtrated and evaporated. The residue was purified using column chromatography on SiO2 affording 2.1 g (68percent) of the title compound.1H NMR (399.988 MHz, CDC13) δ 8.06 - 7.98 (m, 2H), 7.56 (d, J= 8.0 Hz, IH), 7.51 - 7.46 (m, IH), 3.94 (s, 3H), 3.82 (s, 2H)
Reference: [1] Patent: WO2006/589, 2006, A1, . Location in patent: Page/Page column 56-57
[2] Journal of Medicinal Chemistry, 1997, vol. 40, # 25, p. 4030 - 4052
[3] Organic and biomolecular chemistry, 2004, vol. 2, # 12, p. 1732 - 1741
[4] Patent: WO2007/30061, 2007, A1, . Location in patent: Page/Page column 83
  • 6
  • [ 1129-28-8 ]
  • [ 68432-92-8 ]
Reference: [1] Patent: US2009/137595, 2009, A1,
[2] Patent: US2002/2152, 2002, A1,
[3] Patent: US5523302, 1996, A,
[4] Patent: EP1445249, 2004, A1, . Location in patent: Page 136
[5] Patent: US6288120, 2001, B1,
[6] Patent: US6344485, 2002, B1,
  • 7
  • [ 928664-98-6 ]
  • [ 618-89-3 ]
  • [ 68432-92-8 ]
YieldReaction ConditionsOperation in experiment
69% With potassium fluoride; dichloro(1,1'-bis(diphenylphosphanyl)ferrocene)palladium(II)*CH2Cl2 In dimethyl sulfoxide at 130℃; for 18 h; Inert atmosphere; Sealed tube Step 1: To a vial with a stir bar was added methyl 3-bromobenzoate (1.0 equiv.) 4-isoxazoleboronic acid (1.2 equiv.), PdCl2(dppf).CH2Cl2 adduct (0.1 equiv.), 1M KF (2.0) and DMSO (0.10 M). The reaction mixture was degassed with bubbling nitrogen and the vial capped and heated at 130° C. for 18 hr. LCMS analysis indicated the formation of the desired product (MH+-176, Rt—0.62 min). The reaction mixture was diluted with a saturated solution of NH4Cl and extracted with EtOAc (2×). The combined organics were washed with water and brine, dried over MgSO4, filtered and concentrated. The crude material was purified via flash chromatography over silica gel eluting with heptanes and 0-100percent ethyl acetate gradient. Isolated methyl 3-(cyanomethyl)benzoate in 69percent yield. LCMS (m/z) (M+H)=176.1, Rt=0.62). 1H NMR (400 MHz, ) δ ppm 3.92 (s, 3H), 3.99 (s, 2H), 7.49-7.55 (m, 1H), 7.62 (d, J=7.83 Hz, 1H), 7.99 (d, J=7.83 Hz, 1H), 8.04 (s, 1H).
Reference: [1] Patent: US2014/275003, 2014, A1, . Location in patent: Paragraph 0182
  • 8
  • [ 7677-24-9 ]
  • [ 1129-28-8 ]
  • [ 68432-92-8 ]
YieldReaction ConditionsOperation in experiment
43% With tetrabutyl ammonium fluoride In acetonitrile for 20 h; Heating / reflux To an ice-cold solution of methyl 3-bromomethylbenzoate (9.1 g, 40 mmol) in CH3CN (108 mL) was added tetrabutylammonium fluoride (17.3 ML, 60 mmol) and trimethylsilylcyanide (8.0 ML, 60 mmol), and the reaction mixture was heated at reflux for 20 h. The reaction mixture was cooled to room temperature, and the solvent was removed under reduced pressure. Purification by flash column chromatography (silica, 1: 1 EtOAc/hexanes) provided methyl 3-cyanomethylbenzoate as a clear oil (3.0 g, 43percent) :H NMR (300 MHz, DMSO-d6) 8 7.97 (s, 1H), 7.92 (D, J = 8 Hz, 1H), 7.64 (D, J = 8 Hz, 1H), 7.56 (T, J = 8 Hz, 1H), 4.16 (s, 2H), 3.87 (s, 3H).
43% With tetrabutyl ammonium fluoride In acetonitrile for 20 h; Heating / reflux To an ice-cold solution of methyl 3-bromomethylbenzoate (9.1 g, 40 mmol) in CH3CN (108 mL) was added tetrabutylammonium fluoride (17.3 ML, 60 mmol) and trimethylsilylcyanide (8.0 ML, 60 mmol), and the reaction mixture was heated at reflux for 20 h. The reaction mixture was cooled to room temperature, and the solvent was removed under reduced pressure. Purification by flash column chromatography (silica, 1: 1 EtOAc/hexanes) provided methyl 3-cyanomethylbenzoate as a clear oil (3.0 g, 43percent) :H NMR (300 MHz, DMSO-d6) 8 7.97 (s, 1H), 7.92 (D, J = 8 Hz, 1H), 7.64 (D, J = 8 Hz, 1H), 7.56 (T, J = 8 Hz, 1H), 4.16 (s, 2H), 3.87 (s, 3H).
Reference: [1] Synlett, 2009, # 8, p. 1291 - 1294
[2] Patent: WO2005/18557, 2005, A2, . Location in patent: Page/Page column 299
[3] Patent: WO2005/18557, 2005, A2, . Location in patent: Page/Page column 299
  • 9
  • [ 929301-93-9 ]
  • [ 68432-92-8 ]
YieldReaction ConditionsOperation in experiment
32 g With thionyl chloride In chloroform for 8 h; Reflux Weigh m-methoxy formyl phenyl acetic acid 41g,Thionyl chloride 50g,70 reaction 5h,After the reaction,Decompression recovery of thionyl chloride, ice bath,Acid chloride added dropwise ammonia, the reaction overnight,Filtration, cake washing, drying,The filter cake was dissolved in 50 ml of chloroform,Join 20g thionyl chloride,Reflux reaction 8h, after the reaction,The reaction solution was concentrated under reduced pressure,The residue was dissolved in 80 ml of ethyl acetate, washed with water, dried over anhydrous sodium sulfate, filtered,The solvent was recovered under reduced pressure,Under reduced pressure distilled to give a colorless liquid 32g, a yield of 87percent.
Reference: [1] Patent: CN106928092, 2017, A, . Location in patent: Paragraph 0005; 0012
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Reference: [1] Journal of Medicinal Chemistry, 2003, vol. 46, # 3, p. 345 - 348
[2] Chemistry - A European Journal, 2012, vol. 18, # 5, p. 1383 - 1400
[3] Patent: WO2011/47156, 2011, A1,
[4] Journal of Organic Chemistry, 2017, vol. 82, # 2, p. 1114 - 1126
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Reference: [1] Organic and biomolecular chemistry, 2004, vol. 2, # 12, p. 1732 - 1741
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Reference: [1] Organic and biomolecular chemistry, 2004, vol. 2, # 12, p. 1732 - 1741
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Reference: [1] Patent: CN106928092, 2017, A,
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Reference: [1] Patent: CN106928092, 2017, A,
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Reference: [1] Patent: CN106928092, 2017, A,
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  • [ 2084-13-1 ]
YieldReaction ConditionsOperation in experiment
68% at 160℃; for 3 h; 3-Carboxymethylbenzoic Acid 16. Methyl 3-(cyanomethyl)benzoate 15 (6.3 g, 36.0 mmol) was treated with H2SO4 (40percent, 108 mL) and refluxed for 3 h at 160°C. The reaction mixture was then slowly cooled, diluted with cold H20 (108 mL), and filtered. The solid collected was washed with cold H20, dried with vacuum pump, and used without further purification. Yield 4.4 g (68percent). XH-NMR (DMSO): 3.67 s (2H, CH2); 7.44 t (1H, CH), 7.51 dt (1H, CH), 7.82 dt (1H, CH), 7.85 t (1H, CH).
Reference: [1] Patent: WO2012/173784, 2012, A1, . Location in patent: Page/Page column 29
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