Butyl vinyl ether → 8-(1-Butoxyvinyl)-2-(1-phenylcyclopropyl)quinazoline

HRID 1056073Notes

Reaction equation

Br[C:2]1[CH:3]=[CH:4][CH:5]=[C:6]2[C:11]=1[N:10]=[C:9]([C:12]1([C:15]3[CH:20]=[CH:19][CH:18]=[CH:17][CH:16]=3)[CH2:14][CH2:13]1)[N:8]=[CH:7]2.C(=O)([O-])[O-].[K+].[K+].C1(P(C2C=CC=CC=2)CCCP(C2C=CC=CC=2)C2C=CC=CC=2)C=CC=CC=1.[CH:56]([O:58][CH2:59][CH2:60][CH2:61][CH3:62])=[CH2:57]>CN(C=O)C.O.C(O[Pd]OC(=O)C)(=O)C>[CH2:59]([O:58][C:56]([C:2]1[CH:3]=[CH:4][CH:5]=[C:6]2[C:11]=1[N:10]=[C:9]([C:12]1([C:15]3[CH:20]=[CH:19][CH:18]=[CH:17][CH:16]=3)[CH2:14][CH2:13]1)[N:8]=[CH:7]2)=[CH2:57])[CH2:60][CH2:61][CH3:62]

Participants

Conditions

Temperature: 70 °C

Procedure

A solution of 8-bromo-2-(1-phenylcyclopropyl)quinazoline (153.8 mg, 0.473 mmol), diacetoxypalladium (10.62 mg, 0.047 mmol), potassium carbonate (131 mg, 0.946 mmol), 1,3-bis(diphenylphosphino)propane (42.9 mg, 0.104 mmol), and 1-(vinyloxy)butane (0.067 mL, 0.520 mmol) in a mixture of DMF (2.0 mL) and water (0.400 mL) was stirred under argon in a sealed tube at 70° C. for 3 d. The mixture was adsorbed onto silica gel (DMF was removed in vacuo). Chromatographic purification (silica gel, 0-30% EtOAc/hexanes) furnished 8-(1-butoxyvinyl)-2-(1-phenylcyclopropyl)quinazoline (100.0 mg, 0.290 mmol, 61% yield) as a colorless oil: 1H NMR (400 MHz, CDCl3) δ ppm 9.21 (1H, s), 8.16 (1H, dd, J=7.4, 1.4 Hz), 7.73 (1H, dd, J=8.0, 1.4 Hz), 7.43-7.52 (2H, m), 7.32-7.40 (2H, m), 7.26-7.31 (2H, m), 5.32 (1H, d, J=2.0 Hz), 4.41 (1H, d, J=2.0 Hz), 3.81 (2H, t, J=6.5 Hz), 1.82-1.94 (4H, m), 1.69-1.80 (2H, m), 1.47-1.51 (2H, m), 0.93-1.03 (3H, m). m/z (ESI, +ve) 345.2 (M+H)+.

Workup

customChromatographic purification (silica gel, 0-30% EtOAc/hexanes)

Sources & evidence

ORD record: ord-1ad369128e314e1d942af078346c07ec
Source dataset: uspto-grants-2016_07
DOI: 10.6084/m9.figshare.5104873.v1
Patent number: US09394297B2

Reaction notes

Loading…