Formaldehyde → HCID 16068324, compound

Participants

Reaction Steps

A stirred solution/suspension of 1-(4-fluoronaphthalen-1-yl)-3-azabicyclo[3.1.0]hexane (215 mg, 0.95 mmol) in 1,2-dichloromethane (12 mL) was treated with 37% aqueous formaldehyde (0.5 mL, 9.5 mmol), then with sodium triacetoxyborohydride (1.25 g, 4.75 mmol), stirred for 3 h, then treated with 1N sodium hydroxide (5 mL). The organic layer was separated and the aqueous solution was extracted with methylene chloride containing a little 2-propanol (2×10 mL). The combined organic solution was dried (MgSO4) and concentrated in vacuo to afford 1-(4-fluoronaphthalen-1-yl)-3-methyl-3-azabicyclo[3.1.0]hexane (150 mg, 65%, essentially pure without chromatography). This was dissolved in anhydrous ether (5 mL) and treated with 2N HCl/ether (0.35 mL, 0.7 mmol), stirred a few minutes, filtered, rinsed with ether, collected, and dried in vacuo to afford 3-methyl-1-(4-fluoronaphthalen-1-yl)-3-aza-bicyclo[3.1.0]hexane, hydrochloride (150 mg, 82%) as a white solid. MS (M+1) 242.1. 1H NMR (DMSO-d6) δ 0.91-1.01 (m, 1 H) 2.01-2.09 (m, 1 H) 2.13-2.24 (m, 1 H) 2.72-2.84 (m, J=4.69 Hz, 3 H) 3.16-3.30 (m, 1 H) 3.72 (q, J=5.60 Hz, 2 H) 3.93 (dd, J=11.23, 5.17 Hz, 1 H) 7.31 (dd, J=10.74, 8.01 Hz, 1 H) 7.48-7.79 (m, 3 H) 8.07 (d, J=8.20 Hz, 1 H) 8.20 (d, J=8.40 Hz, 1 H). 13C (DMSO-d6) δ 14.51, 22.36, 29.97, 56.72, 60.47, 109.90, 121.34, 123.61, 125.04, 127.43, 128.50, 131.39, 134.24 157.08.

Provenance & Evidence