Hydrochloric Acid → Methyl 2-methyl-3-[4-[2-(2,3-dihydro-1,4-benzoxazin-4-yl)ethoxy]phenyl]-2-ethoxypropanoate

HRID 393550Notes

Reaction equation

[O:1]1[C:6]2[CH:7]=[CH:8][CH:9]=[CH:10][C:5]=2[N:4]([CH2:11][CH2:12][O:13][C:14]2[CH:19]=[CH:18][C:17]([CH2:20][CH:21]([O:26][CH2:27][CH3:28])[C:22]([O:24][CH3:25])=[O:23])=[CH:16][CH:15]=2)[CH2:3][CH2:2]1.[CH:29]([N-]C(C)C)(C)C.[Li+].CI.Cl>O1CCCC1.O>[CH3:29][C:21]([O:26][CH2:27][CH3:28])([CH2:20][C:17]1[CH:16]=[CH:15][C:14]([O:13][CH2:12][CH2:11][N:4]2[C:5]3[CH:10]=[CH:9][CH:8]=[CH:7][C:6]=3[O:1][CH2:2][CH2:3]2)=[CH:19][CH:18]=1)[C:22]([O:24][CH3:25])=[O:23]

Participants

Conditions

Temperature: -78 °C

Procedure

To a solution of methyl 3-[4-[2-(2,3-dihydro-1,4-benzoxazin-4-yl)ethoxy]phenyl]-2-ethoxypropanoate (0.6 g, 1.5 mmol) obtained in example 2 in dry tetrahydrofuran (5 mL) was added lithium diisopropyl amide (5.25 μL, 0.5 mL solution in THF/hexane) at −78° C. After stirring for 1 h at −78° C., methyl iodide (0.75 mL) was added and the reaction mixture was allowed to warm to room temperature (ca 25° C.) and stirred for further 20 h at the same temperature. Water (20 mL) was added, acidified with 1 N hydrochloric acid and extracted with ethyl acetate (2×25 mL). The combined ethyl acetate layer was washed with water (25 mL), brine (25 mL), dried (Na2SO4), filtered and the solvent was evaporated under reduced pressure to afford the title compound (0.5 g, 80%) as an oil.

Workup

temperatureto warm to room temperature (ca 25° C.)
stirringstirred for further 20 h at the same temperature
extractionextracted with ethyl acetate (2×25 mL)
washThe combined ethyl acetate layer was washed with water (25 mL), brine (25 mL)
dry with materialdried (Na2SO4)
filtrationfiltered
customthe solvent was evaporated under reduced pressure

Sources & evidence

ORD record: ord-d0e0f18f558f4887b123b1e89484c831
Source dataset: uspto-grants-2004_10
DOI: 10.6084/m9.figshare.5104873.v1
Patent number: US06809095B2

Reaction notes

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