Iodoethane → 8-Ethoxy-2-methyl-3-oxo-3,4-dihydro-2H-benzo[b][1,4]oxazine-6-carbaldehyde

HRID 1184513Notes

Reaction equation

[OH:1][C:2]1[C:7]2[O:8][CH:9]([CH3:13])[C:10](=[O:12])[NH:11][C:6]=2[CH:5]=[C:4]([CH:14]=[O:15])[CH:3]=1.C(=O)([O-])[O-].[Cs+].[Cs+].I[CH2:23][CH3:24]>CN(C=O)C>[CH2:23]([O:1][C:2]1[C:7]2[O:8][CH:9]([CH3:13])[C:10](=[O:12])[NH:11][C:6]=2[CH:5]=[C:4]([CH:14]=[O:15])[CH:3]=1)[CH3:24]

Participants

Conditions

Temperature: 23 °C

Procedure

To a 20 mL screw cap vial was added 8-hydroxy-2-methyl-3-oxo-3,4-dihydro-2H-benzo[b][1,4]oxazine-6-carbaldehyde 398A (0.619 g, 2.99 mmol) and cesium carbonate (0.973 g, 2.99 mmol). The mixture was suspended in DMF (5.98 mL) and then cooled in an ice bath. Iodoethane (0.241 mL, 2.99 mmol) was added in 2 portions over 5 minutes. The reaction mixture was stirred for 2 hr, slowly warmed to 23° C., and the stirred for 18 hr. The crude material was purified by prep HPLC-MS (30-50% MeCN in water, basic mode) and the fractions were collected and concentrated in vacuo. The resulting solid was isolated by filtration, washed with water and dried in vacuo to give a tan solid (0.404 g, 57% yield): 1H NMR (400 MHz, DMSO-d6) δ ppm 1.36 (t, J=6.95 Hz, 3H) 1.46 (d, J=6.82 Hz, 3H) 4.14 (qd, J=6.99, 1.77 Hz, 2H) 4.72-4.88 (m, 1H) 7.07 (d, J=1.77 Hz, 1H) 7.24 (d, J=1.77 Hz, 1H) 9.82 (s, 1H) 10.92 (s, 1H). ESI-MS: m/z 236.1 (M+H)+.

Workup

customTo a 20 mL screw cap
temperaturecooled in an ice bath
stirringthe stirred for 18 hr
customThe crude material was purified by prep HPLC-MS (30-50% MeCN in water, basic mode)
customthe fractions were collected
concentrationconcentrated in vacuo
customThe resulting solid was isolated by filtration
washwashed with water
customdried in vacuo

Sources & evidence

ORD record: ord-cc365418b19a46cc83b554dda8963b33
Source dataset: uspto-grants-2014_03
DOI: 10.6084/m9.figshare.5104873.v1
Patent number: US08669249B2

Reaction notes

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