1,4-Dioxane → 1-(4,5-Dihydro-1H-imidazol-2-yl)isochroman-5-ol

HRID 1771412Notes

Reaction equation

Br[C:2]1[CH:11]=[CH:10][CH:9]=[C:8]2[C:3]=1[CH2:4][CH2:5][O:6][CH:7]2[C:12]1[NH:13][CH2:14][CH2:15][N:16]=1.B1(B2OC(C)(C)C(C)(C)O2)OC(C)(C)C(C)(C)[O:18]1.C([O-])(=O)C.[K+].O1CCOCC1>CC(C)([P](C(C)(C)C)([Pd][P](C(C)(C)C)(C(C)(C)C)C(C)(C)C)C(C)(C)C)C.CN(C=O)C>[NH:13]1[CH2:14][CH2:15][N:16]=[C:12]1[CH:7]1[C:8]2[CH:9]=[CH:10][CH:11]=[C:2]([OH:18])[C:3]=2[CH2:4][CH2:5][O:6]1

Participants

Conditions

Temperature: 160 °C

Procedure

A mixture of 2-(5-bromoisochroman-1-yl)-4,5-dihydro-1H-imidazole (720 mg), bis(pinacolato)diboron (715 mg) bis(tri-t-butylphosphine)palladium(0) (39 mg), potassiumacetate (503 mg), dioxane (9 ml) and DMF (0.75 ml) was stirred under inert atmosphere in microwave reactor at 160° C. for 30 minutes. Additional bis(tri-t-butylphosphine)palladium(0) (21 mg) was added and heating continued for 15 minutes. The intermediate 2-(5-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)isochroman-1-yl)-4,5-dihydro-1H-imidazole (680 mg) was purified with separation method A and stirred with EtOAc (2 ml), water (2 mil) and hydrogen peroxide (35%, 0.07 ml) at ice bath temperature for 2 hrs. The title compound was purified with separation methods A and E. (Yield 45 mg).

Workup

temperatureheating
waitcontinued for 15 minutes
customThe intermediate 2-(5-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)isochroman-1-yl)-4,5-dihydro-1H-imidazole (680 mg) was purified with separation method A
stirringstirred with EtOAc (2 ml), water (2 mil) and hydrogen peroxide (35%, 0.07 ml) at ice bath temperature for 2 hrs
customThe title compound was purified with separation methods A and E

Sources & evidence

ORD record: ord-fceb03cb4e514b22ae649864b2cb8b0f
Source dataset: uspto-grants-2016_02
DOI: 10.6084/m9.figshare.5104873.v1
Patent number: US09249127B2

Reaction notes

Loading…