1-{2-[4-(10-methoxy-5H,7H-6-oxa-12-thia-dibenzo[a,e]azulen-7-yl)-phenoxy]-ethyl)-piperidine → 7-[4-(2-piperidin-1-yl-ethoxy)-phenyl]-5H,7H-6-oxa-12-thia-dibenzo[a,e]azulen-10-ol

HRID 916858Notes

Reaction equation

C[O:2][C:3]1[CH:35]=[CH:34][C:6]2[C:7]3[CH:8]([C:19]4[CH:33]=[CH:32][C:22]([O:23][CH2:24][CH2:25][N:26]5[CH2:31][CH2:30][CH2:29][CH2:28][CH2:27]5)=[CH:21][CH:20]=4)[O:9][CH2:10][C:11]4[CH:18]=[CH:17][CH:16]=[CH:15][C:12]=4[C:13]=3[S:14][C:5]=2[CH:4]=1>CN1C(=O)CCC1.C(Cl)Cl>[N:26]1([CH2:25][CH2:24][O:23][C:22]2[CH:21]=[CH:20][C:19]([CH:8]3[C:7]4[C:6]5[CH:34]=[CH:35][C:3]([OH:2])=[CH:4][C:5]=5[S:14][C:13]=4[C:12]4[CH:15]=[CH:16][CH:17]=[CH:18][C:11]=4[CH2:10][O:9]3)=[CH:33][CH:32]=2)[CH2:31][CH2:30][CH2:29][CH2:28][CH2:27]1

Participants

Conditions

Temperature: 170 °C

Procedure

Add NaSEt (92 mg, 1.1 mmol) to a solution of 1-{2-[4-(10-methoxy-5H,7H-6-oxa-12-thia-dibenzo[a,e]azulen-7-yl)-phenoxy]-ethyl}-piperidine (266 mg, 0.55 mmol) in NMP (3 mL). Heat to 170° C. for 20 min. Add additional NaSEt (92 mg, 1.1 mmol) and continue heating for 1 h. Quench the reaction with water and dilute with CH2Cl2. Wash the organic phase with water and brine, dry over MgSO4, filter and concentrate. Purify the crude product by flash chromatography (0-10% (2M NH3 in MeOH)/CH2Cl2) followed by preparative HPLC to afford 7-[4-(2-piperidin-1-yl-ethoxy)-phenyl]-5H,7H-6-oxa-12-thia-dibenzo[a,e]azulen-10-ol (16.3 mg, 6.3%)

Workup

additionAdd additional NaSEt (92 mg, 1.1 mmol)
temperaturecontinue heating for 1 h
customQuench
customthe reaction with water
washWash the organic phase with water and brine
dry with materialdry over MgSO4
filtrationfilter
concentrationconcentrate
customPurify the crude product by flash chromatography (0-10% (2M NH3 in MeOH)/CH2Cl2)

Sources & evidence

ORD record: ord-f09af0844acf4c7bbbc660ee47942194
Source dataset: uspto-grants-2007_09
DOI: 10.6084/m9.figshare.5104873.v1
Patent number: US07271264B2

Reaction notes

Loading…