Morpholine → [1-(3-Morpholin-4-yl-phenyl)ethyl]carbamic acid tert-butyl ester

HRID 2307418Notes

Reaction equation

[C:1]([O:5][C:6]([NH:8][CH:9]([C:11]1[CH:12]=[C:13](OS(C(F)(F)F)(=O)=O)[CH:14]=[CH:15][CH:16]=1)[CH3:10])=[O:7])([CH3:4])([CH3:3])[CH3:2].[NH:25]1[CH2:30][CH2:29][O:28][CH2:27][CH2:26]1.P([O-])([O-])([O-])=O.[K+].[K+].[K+]>ClCCl>[C:1]([O:5][C:6](=[O:7])[NH:8][CH:9]([C:11]1[CH:16]=[CH:15][CH:14]=[C:13]([N:25]2[CH2:30][CH2:29][O:28][CH2:27][CH2:26]2)[CH:12]=1)[CH3:10])([CH3:4])([CH3:3])[CH3:2]

Participants

Conditions

Temperature: 80 °C

Procedure

A mixture of trifluoro-methanesulfonic acid 3-(1-tert-butoxycarbonylaminoethyl)phenyl ester (1.5 g, 4.08 mmol), morpholine (8 mL) Pd2(dba)3 (187 mg, 5 mol %), di-t-butyl-biphenylphosphine (243 mg, 20 mol %), potassium phosphate (1.21 g, 5.71 mmol) was stirred at 80° C. in a sealed tube for 10 hours. After cooling down, the reaction mixture was diluted with dichloromethane (50 mL) and washed with water (10 mL). The aqueous layer was extracted with dichloromethane (2×15 mL) and the combined organic layer was dried over magnesium sulfate and concentrated under vacuum. The crude product was purified by flash chromatography of Biotage with 30% ethyl acetate/hexanes to provide the title compound as a pale yellow solid (1.01 g, 81% yield).

Workup

temperatureAfter cooling down
washwashed with water (10 mL)
extractionThe aqueous layer was extracted with dichloromethane (2×15 mL)
dry with materialthe combined organic layer was dried over magnesium sulfate
concentrationconcentrated under vacuum
customThe crude product was purified by flash chromatography of Biotage with 30% ethyl acetate/hexanes

Sources & evidence

ORD record: ord-bc23ea6c09be49498922e6282e198ea3
Source dataset: uspto-grants-2004_12
DOI: 10.6084/m9.figshare.5104873.v1
Patent number: US06831080B2

Reaction notes

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