Sodium hydride → ethyl 4-methoxy-3-(N-(2-morpholinoethyl)-methylsulfonamido)-phenyl carbonate

HRID 1776589Notes

Reaction equation

[C:1](=[O:19])([O:5][C:6]1[CH:11]=[CH:10][C:9]([O:12][CH3:13])=[C:8]([NH:14][S:15]([CH3:18])(=[O:17])=[O:16])[CH:7]=1)[O:2][CH2:3][CH3:4].[H-].[Na+].Cl.Cl[CH2:24][CH2:25][N:26]1[CH2:31][CH2:30][O:29][CH2:28][CH2:27]1>CN(C=O)C.C(Cl)Cl>[C:1](=[O:19])([O:5][C:6]1[CH:11]=[CH:10][C:9]([O:12][CH3:13])=[C:8]([N:14]([CH2:24][CH2:25][N:26]2[CH2:31][CH2:30][O:29][CH2:28][CH2:27]2)[S:15]([CH3:18])(=[O:16])=[O:17])[CH:7]=1)[O:2][CH2:3][CH3:4]

Participants

Conditions

Temperature: 90 °C

Procedure

A solution of ethyl 4-methoxy-3-(methylsulfonamido)phenyl carbonate (0.850 g, 2.94 mmol) in dry DMF (15 ml) was cooled to 0° C. under nitrogen atmosphere, and sodium hydride (60% w/w, 0.300 g, 7.50 mmol) was added portion-wise. After 10 minutes, the cold bath was removed, 4-(2-chloroethyl)morpholine hydrochloride (0.680 mg, 3.65 mmol) was added, and the mixture was heated to 90° C. for 2 hours. After cooling to RT, the reaction mixture was diluted with DCM and washed with water. The organic layer was washed with brine and dried over Na2SO4; the solvent was evaporated and the crude was purified by flash chromatography on silica gel column (DCM:MeOH=10:0.1) affording ethyl 4-methoxy-3-(N-(2-morpholinoethyl)methylsulfonamido)-phenyl carbonate (0.250 g, 0.621 mmol, 21.14% yield, UPLC-MS purity: 97%, MS/ESI+ 403.1 [MH]+).

Workup

customthe cold bath was removed
temperatureAfter cooling to RT
washwashed with water
washThe organic layer was washed with brine
dry with materialdried over Na2SO4
customthe solvent was evaporated
customthe crude was purified by flash chromatography on silica gel column (DCM:MeOH=10:0.1)

Sources & evidence

ORD record: ord-a4d1214d3fd24512aeacee0f5da23569
Source dataset: uspto-grants-2016_02
DOI: 10.6084/m9.figshare.5104873.v1
Patent number: US09265768B2

Reaction notes

Loading…