3-Cyano-5-fluorobenzaldehyde

3 -fluoro-5 -formylbenzonitrile : A solution of 3 -bromo-5 -fluorobenzonitrile(5.00 g, 25.0 mmol) in dry THF (25 mL) was cooled to 0 °C and 2M iPrMgCl (15.0 mL, 30.0 mmol) in THF was added dropwise over 5 minutes. The mixture was stirred at 0 °C for 15 minutes then at ambient temperature for 1 hour. The mixture was cooled to 0 °C and dry DMF (5.81 mL, 75.0 mmol) was added. The mixture was stirred for 17 hours during which time the temperature reached ambient temperature after 2 hours. The mixture was added to ice water (150 mL) and EtStep A: 3-fluoro-5-formylbenzonitrile: A solution of 3-bromo-5- fluorobenzonitrile (5.00 g, 25.0 mmol) in dry THF (25 mL) was cooled to 0 °C and 2M iPrMgCl (15.0 mE, 30.0 mmol) in THF was added dropwise over 5 minutes. The mixture was stirred at 0 °C for 15 minutes then at ambient temperature for 1 hour. The mixture was cooled to 0 °C and dry DMF (5.81 mL, 75.0 mmol) was added. The mixture was stirred for 17 hours during which time the temperature reached ambient temperature after 2 hours. The mixture was added to ice water (150 mL) and Et20 (100 mL). The biphasic mixture was stirred and treated with 6M HC1 to aqueous pH=3. The organic layer was removed and the aqueous layer extracted with Et20 (2X). The combined Et20 fractions were washed with saturated NaC1 and dried over MgSO4/activated carbon. The dried solution was filtered through a Si02 plug eluting with Et20. The filtrate was concentrated to give the title compound as a yellow solid that was dried in vacuum (3.68 g, 99percent). ‘H NMR (CDC13) ö 10.0 (s, 1H), 8.00 (s, 111), 7.81-7.86 (m, 111), 7.62-7.67 (m, 111).1003751 Step A: 3-fluoro-5-formylbenzonitrile: A solution of 3-bromo-5- fluorobenzonitrile (5.00 g, 25.0 mmol) in dry THF (25 mL) was cooled to 0 °C and 2M iPrMgCl (15.0 mE, 30.0 mmol) in TUF was added dropwise over 5 minutes. The mixture was stirred at 0 °C for 15 minutes then at ambient temperature for 1 hour. The mixture was cooled to 0 °C and dry DMF (5.81 mL, 75.0 mmol) was added. The mixture was stirred for 17 hours during which time the temperature reached ambient temperature after 2 hours. The mixture was added to ice water (150 mE) and Et20 (100 mE). The biphasic mixture was stirred and treated with 6M HC1 to aqueous pH=3. The organic layer was removed and the aqueous layer extracted with Et20 (2X). The combined Et20 fractions were washed with saturated NaC1 and dried over MgSO4/activated carbon. The dried solution was filtered through a Si02 plug eluting with Et20. The filtrate was concentrated to give the title compound as a yellow solid that was dried in vacuum (3.68 g, 99percent). ‘H NMR (CDCI3) 8 10.0 (s, 1H), 8.00 (s, 1H), 7.81- 7.86 (m, 111), 7.62-7.67 (m, 1H).Preparation 0-100 Trans-3-(4-amino- 1 -(2-methoxyethyl)pyrrolidin-3-yl)-5-fluorobenzonitrile 1005731 Step A: 3-fluoro-5-fonnylbenzonitrile: A solution of 3-bromo-5- fluorobenzonitrile (5.00 g, 25.0 mmol) in dry THF (25 mL) was cooled to 0 °C and 2M iPrMgCl (15.0 mL, 30.0 mmol) in THF was added dropwise over 5 minutes. The mixture was stirred at 0 °C for 15 minutes then at ambient temperature for 1 hour. The mixture was cooled to 0 °C and dry DMF (5.81 mL, 75.0 mmol) was added. The mixture was stirred for 17 hours during which time the temperature reached ambient temperature after 2 hours. The mixture was added to ice water (150 mL) and Et20 (100 mE). The biphasic mixture was stirred and treated with 6M HC1 to aqueous pH=3. The organic layer was removed and the aqueous layer extracted with Et20 (2X). The combined Et20 fractions were washed with saturated NaCl and dried over MgSO4lactivated carbon. The dried solution was filtered through a Si02 plug eluting with Et20. The filtrate was concentrated to give the title compound as a yellow solid that was dried in vacuum (3.68 g, 99percent). ‘H NMR (CDC13) ö 10.0 (s, 1H), 8.00 (s, 1H), 7.81- 7.86 (m, 1H), 7.62-7.67 (m, 1H).INTERMEDIATE 80 PREPARATION OF 3-FLUORO-5-[(1E)-3-OXOPROP-1-EN-1-YL]BENZONITRILE A mixture of

Molecular Weight:149.12
XLogP3:1.2
Hydrogen Bond Acceptor Count:3
Rotatable Bond Count:1
Exact Mass:149.027691913
Monoisotopic Mass:149.027691913
Topological Polar Surface Area:40.9
Heavy Atom Count:11
Complexity:196
Covalently-Bonded Unit Count:1
Compound Is Canonicalized:Yes