Carbamic acid, ethyl-, ethyl ester → HCID 58266356, compound

HRID 1888440Notes

Reaction equation

[Br:1][C:2]1[CH:16]=[CH:15][C:5]([CH2:6][N:7]2[CH2:12][C@H:11]([CH3:13])[O:10][C@H:9]([CH3:14])[CH2:8]2)=[C:4](F)[CH:3]=1.C(NC([O:23][CH2:24][CH3:25])=O)C.[H-].[Na+]>O1CCOCC1>[Br:1][C:2]1[CH:16]=[CH:15][C:5]([CH2:6][N:7]2[CH2:12][C@H:11]([CH3:13])[O:10][C@H:9]([CH3:14])[CH2:8]2)=[C:4]([O:23][CH2:24][CH3:25])[CH:3]=1

Participants

Conditions

Temperature: 100 °C

Procedure

To a solution of cis 4-(4-bromo-2-fluorobenzyl)-2,6-dimethylmorpholine (0.76 g, 2.5 mmol) in 1,4-dioxane (7.5 mL) under nitrogen was added ethyl urethane (1.2 mL, 10.0 mmol) followed by portionwise addition of sodium hydride (60% dispersion in mineral oil, 0.40 g, 10.0 mmol). The reaction mixture was heated at 100° C. for 24 h then partitioned between DCM and water and the phases were separated. The aqueous phase was further extracted with DCM and the combined organic layers were dried over sodium sulfate, filtered and evaporated. The residue was purified by flash chromatography (silica, 80 g column, ISCO, 0-100% ethyl acetate in pentane) to afford the title compound (0.114 g, 14%). 1H NMR (CD3OD and CDCl3, 300 MHz): 7.22 (d, J=8.0 Hz, 1H), 7.05 (dd, J=8.1, 1.9 Hz, 1 H), 6.97 (d, J=1.9 Hz, 1H), 4.01 (q, J=7.0 Hz, 2H), 3.75-3.62 (m, 2H), 3.47 (s, 2 H), 2.75-2.66 (m, 2H), 1.86-1.76 (m, 2H), 1.41 (t, J=7.0 Hz, 3H), 1.14 (d, J=6.3 Hz, 6H). LCMS (Method G): RT=3.24 min, M+H+=328.

Workup

customthen partitioned between DCM and water
customthe phases were separated
extractionThe aqueous phase was further extracted with DCM
dry with materialthe combined organic layers were dried over sodium sulfate
filtrationfiltered
customevaporated
customThe residue was purified by flash chromatography (silica, 80 g column, ISCO, 0-100% ethyl acetate in pentane)

Sources & evidence

ORD record: ord-aa327d618dfb4c4291412c26f416f496
Source dataset: uspto-grants-2013_08
DOI: 10.6084/m9.figshare.5104873.v1
Patent number: US08501765B2

Reaction notes

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