Cesium carbonate → methyl 3-bromo-2-methyl-6-[2-(tetrahydro-2H-pyran-2-yloxy)ethoxy]benzoate

HRID 577462Notes

Reaction equation

[Br:1][C:2]1[C:3]([CH3:13])=[C:4]([C:9]([OH:12])=[CH:10][CH:11]=1)[C:5]([O:7][CH3:8])=[O:6].C(=O)([O-])[O-].[Cs+].[Cs+].Br[CH2:21][CH2:22][O:23][CH:24]1[CH2:29][CH2:28][CH2:27][CH2:26][O:25]1>CN(C=O)C.C(OCC)(=O)C>[Br:1][C:2]1[C:3]([CH3:13])=[C:4]([C:9]([O:12][CH2:21][CH2:22][O:23][CH:24]2[CH2:29][CH2:28][CH2:27][CH2:26][O:25]2)=[CH:10][CH:11]=1)[C:5]([O:7][CH3:8])=[O:6]

Participants

Conditions

Temperature: 55 °C

Procedure

A solution of methyl 3-bromo-6-hydroxy-2-methylbenzoate (Cpd GG, 1.94 g, 7.90 mmol) in DMF (25 mL) was treated with cesium carbonate (3.45 g, 10.0 mmol) and then 2-(2-bromoethoxy)tetrahydro-2H-pyran (2.06 g, 9.84 mmol). The reaction mixture was heated at 55° C. for 16 hours. The reaction mixture was cooled to room temperature, diluted with ethyl acetate, and washed with water (2×) and brine. The organic layer was concentrated under vacuum to give a brown oil which was purified by column chromatography (0-25%, ethyl acetate/heptane) to give the title compound (Cpd HH, 2.11 g, 67% yield) as a clear oil. 1H NMR (400 MHz, chloroform-d) δ 7.50 (d, J=8.80 Hz, 1H), 6.72 (d, J=8.80 Hz, 1H), 4.68 (t, J=3.36 Hz, 1H), 4.13-4.18 (m, 2H), 4.00 (td, J=4.77, 11.37 Hz, 1H), 3.91 (s, 3H), 3.86 (ddd, J=3.06, 8.59, 11.34 Hz, 1H), 3.74-3.80 (m, 1H), 3.49-3.56 (m, 1H), 2.32 (s, 3H), 1.78-1.89 (m, 1H), 1.67-1.77 (m, 1H), 1.58-1.66 (m, 2H), 1.49-1.55 (m, 2H).

Workup

temperatureThe reaction mixture was cooled to room temperature
washwashed with water (2×) and brine
concentrationThe organic layer was concentrated under vacuum
customto give a brown oil which
customwas purified by column chromatography (0-25%, ethyl acetate/heptane)

Sources & evidence

ORD record: ord-a0f7183ec5f349b4b4a7bdcf654f0b3d
Source dataset: uspto-grants-2015_05
DOI: 10.6084/m9.figshare.5104873.v1
Patent number: US09040515B2

Reaction notes

Loading…