Reaction #7887

Reaction equation

2-[4-(5-chloropyridin-2-yl)-3-methoxyphenyl]-1,3-benzoxazole

morpholine

1,1′-biphenyl-2-yl[di(tert-butyl)]phosphine

NaOtBu

→

2-[3-methoxy-4-(5-morpholin-4-ylpyridin-2-yl)phenyl]-1,3-benzoxazole

Conditions

Workup

1. 1
   Otherevacuated
2. 2
   workup.ADDITIONToluene (800 μL) was added
3. 3
   Otherthe mixture was degassed with a stream of argon for 5 min
4. 4
   OtherThe tube was sealed
5. 5
   Otherpurified by automated flash chromatography

Procedure

2-[4-(5-chloropyridin-2-yl)-3-methoxyphenyl]-1,3-benzoxazole (58 mg, 0.17 mmol), morpholine (18 μL, 0.21 mmol), Pd(OAc)2 (0.38 mg, 0.0017 mmol), 1,1′-biphenyl-2-yl[di(tert-butyl)]phosphine (1.0 mg, 0.0034 mmol), and NaOtBu (23 mg, 0.24 mmol) were combined in a sealable tube evacuated and backfilled with argon. Toluene (800 μL) was added and the mixture was degassed with a stream of argon for 5 min. The tube was sealed and the mixture was heated to 110° C. for 18 h. Crude mixture was adsorbed onto silica gel and purified by automated flash chromatography using an EtOAc/hexanes gradient to afford 2-[3-methoxy-4-(5-morpholin-4-ylpyridin-2-yl)phenyl]-1,3-benzoxazole as a yellow solid. The freebase was dissolved in Et2O/CH2Cl2 and treated with 1N HCl in Et2O. Resulting yellow solid was filtered and dried under high vacuum to afford the desired 2-[3-methoxy-4-(5-morpholin-4-ylpyridin-2-yl)phenyl]-1,3-benzoxazole hydrochloride as a yellow solid: 1H NMR (CD3OD, 300 MHz) δ 8.33–8.30 (d, 1H), 8.20–8.09 (m, 2H), 8.08–8.02 (m, 2H), 7.87–7.77 (m, 2H), 7.75–7.71 (m, 1H), 7.53–7.42 (m, 2H), 4.10 (s, 3H), 3.89 (t, 4H), 3.49–3.47 (t, 4H). MS (ESI) 388 (M+H)+.

Source