Sodium Carbonate → 3-(2-methyl-3-oxo-3,4-dihydro-2H-benzo[b][1,4]oxazin-6-yl)benzoic acid

HRID 1184439Notes

Reaction equation

Br[C:2]1[CH:13]=[CH:12][C:5]2[O:6][CH:7]([CH3:11])[C:8](=[O:10])[NH:9][C:4]=2[CH:3]=1.[C:14]([C:17]1[CH:18]=[C:19](B(O)O)[CH:20]=[CH:21][CH:22]=1)([OH:16])=[O:15].C([O-])([O-])=O.[Na+].[Na+]>CN(C=O)C.C1C=CC([P]([Pd]([P](C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)([P](C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)[P](C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)=CC=1>[CH3:11][CH:7]1[O:6][C:5]2[CH:12]=[CH:13][C:2]([C:21]3[CH:22]=[C:17]([CH:18]=[CH:19][CH:20]=3)[C:14]([OH:16])=[O:15])=[CH:3][C:4]=2[NH:9][C:8]1=[O:10]

Participants

Conditions

Temperature: 80 °C

Procedure

To a 20 mL screw cap vial was added 6-bromo-2-methyl-2H-benzo[b][1,4]oxazin-3(4H)-one 19 (100 mg, 0.5 mmol), 3-carboxy phenylboronic acid (91 mg, 0.55 mmol), Pd(PPh3)4 (17 mg, 0.015 mmol), and aqueous Na2CO3 (2M, 0.62 mL, 1.25 mmol) in DMF (4 mL). The reaction was heated at 80° C. overnight then cooled and filtered. The filtrate was purified by preparative HPLC-MS (15-60% MeCN in water). The appropriate fractions were combined and concentrated in vacuo to give a white solid: 1H NMR (DMSO-d6, 400 MHz): δ=13.11 (br. s., 1H), 10.72 (s, 1H), 8.09 (t, J=1.6 Hz, 1H), 7.91 (dt, J=7.6, 1.4 Hz, 1H), 7.80-7.85 (m, 1H), 7.54-7.62 (m, 1H), 7.27 (dd, J=8.3, 2.3 Hz, 1H), 7.20 (d, J=2.0 Hz, 1H), 7.07 (d, J=8.3 Hz, 1H), 4.69-4.77 (m, 1H), 1.45 ppm (d, J=6.8 Hz, 3H). ESI-MS: m/z 284.2 (M+H)+.

Workup

customTo a 20 mL screw cap
temperaturethen cooled
filtrationfiltered
customThe filtrate was purified by preparative HPLC-MS (15-60% MeCN in water)
concentrationconcentrated in vacuo
customto give a white solid

Sources & evidence

ORD record: ord-a549681dd31849498424d71e2d06a67d
Source dataset: uspto-grants-2014_03
DOI: 10.6084/m9.figshare.5104873.v1
Patent number: US08669249B2

Reaction notes

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