3-(CYANOMETHYL)BENZOICACID

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).General procedure: A 25-mL flask was charged with Pd(OAc)To a solution Intermediate 2 (200 mg) in DCM (10 mL) was added 4-(cyanomethyl)benzoic acid (47.0 mg, 0.292 mmol) and EDCI (84 mg, 0.438 mmol), HOBT (67.4 mg, 0.438 mmol), TEA (88.5 mg, 0.876 mmol) at room temperature. After stirring at room temperature 16 h, the mixture was concentrated to give a residue which was purified by prep-HPLC (Waters 2767/Qda, Column: SunFire 19*250mm 10um, Mobile Phase A: 0.1%TFA/H20, B: ACN) to give Compound 20 (65 mg) (a TFA salt) as yellow oil. Compound 20 'H NMR MeOH-d4 (400 MHz):6 8.42 (s, 1H), 7.85 (d, J= 8.0 Hz, 2H), 7.51 (s, 1H), 7.46 (d, J= 8.4Hz, 2H), 4.45-4.41 (m, 5H), 4.00-3.91 (m, 4H), 2.54-2.48 (m, 1H), 2.22-2.03 (m, 4H), 1.83-1.77 (m, 1H).To a solution of intermediate 2 (200 mg) in DCM (10 mL) wasadded To a solution of intermediate 3 (200 mg) in DCM (10 mL) was added General procedure: A 25-mL flask was charged with Pd(OAc)2 (1.2 mg, 0.005 mmol), 1-iodo-4-nitrobenzene (1a, 127.0 mg, 0.5 mmol), K2CO3 (141.0 mg, 1.0 mmol), H2O (0.5 mL), and PEG 400 (2.0 mL); the flask was subjected to standard cycles (3 ×) of evacuation and back-filling with dry and pure CO. The mixture was stirred at r.t. for the indicated time. The mixture was poured into sat. aq NaCl (15 mL), acidified to pH 3 with 3 M aq HCl, and extracted with EtOAc (3 × 15 mL). The solvent was removed from the combined organic phases on a rotary evaporator. The crude product was purified by column chromatography (silica gel, PE'EtOAc'HCO2H, 25:1:1) to afford 2a as a light yellow solid; yield: 75mg (90percent); mp 238.0'239.3 °C. 1H NMR (400 MHz, DMSO-d6): delta = 13.68 (br s, 1 H), 8.30 (d, J = 8.0 Hz, 2 H), 8.14 (d, J = 8.0 Hz, 2 H). 13C NMR (100 MHz, DMSO-d6): delta = 165.9, 150.0, 136.4, 130.7, 123.8.

3-(Cyanomethyl)benzoic Acid is a reagent used in the synthesis of various pharmaceutically important compounds, such as its use in the synthesis of neprilysin inhibitors.

Molecular Weight:161.16
XLogP3:1.3
Hydrogen Bond Donor Count:1
Hydrogen Bond Acceptor Count:3
Rotatable Bond Count:2
Exact Mass:161.047678466
Monoisotopic Mass:161.047678466
Topological Polar Surface Area:61.1
Heavy Atom Count:12
Complexity:216
Covalently-Bonded Unit Count:1
Compound Is Canonicalized:Yes