Sodium Hydroxide → 2-Methoxy-6-(pyrimidin-2-yl)benzoic acid

HRID 869014Notes

Reaction equation

[CH3:1][O:2][C:3]1[CH:12]=[CH:11][CH:10]=[C:9]([C:13]2[N:18]=[CH:17][CH:16]=[CH:15][N:14]=2)[C:4]=1[C:5]([O:7]C)=[O:6].[OH-].[Na+]>C1COCC1>[CH3:1][O:2][C:3]1[CH:12]=[CH:11][CH:10]=[C:9]([C:13]2[N:14]=[CH:15][CH:16]=[CH:17][N:18]=2)[C:4]=1[C:5]([OH:7])=[O:6]

Participants

Conditions

Temperature: 50 °C

Procedure

To a solution of the title compound of Step A (265 mg, 1.09 mmol) in THF (4 mL) was added 2 M NaOH (2 mL). The mixture was heated at 50° C. for 72 h. The reaction mixture was cooled to room temperature and concentrated in vacuo to remove THF. Then, 1 M HCl(aq) was added and the aqueous was extracted with 10:1 DCM/2,2,2-trifluoroethanol (3×). The combined organic layers were dried over Na2SO4, filtered and concentrated to give intermediate A-24, which was used without further purification in subsequent steps. MS (ESI) mass calcd. for C12H10N2O3, 230.1. m/z found 231.1 [M+H]+. 1H NMR (500 MHz, DMSO-d6) δ 12.63 (s, 1H), 8.86 (d, J=4.9 Hz, 2H), 7.77 (dd, J=7.9, 1.0 Hz, 1H), 7.51 (t, J=8.1 Hz, 1H), 7.45 (t, J=4.9 Hz, 1H), 7.25 (dd, J=8.4, 1.0 Hz, 1H), 3.83 (s, 3H).

Workup

temperatureThe reaction mixture was cooled to room temperature
concentrationconcentrated in vacuo
customto remove THF
additionThen, 1 M HCl(aq) was added
extractionthe aqueous was extracted with 10:1 DCM/2,2,2-trifluoroethanol (3×)
dry with materialThe combined organic layers were dried over Na2SO4
filtrationfiltered
concentrationconcentrated
customto give intermediate A-24, which
customwas used without further purification in subsequent steps

Sources & evidence

ORD record: ord-e8c67575047246eba569f44991da6fa9
Source dataset: uspto-grants-2015_03
DOI: 10.6084/m9.figshare.5104873.v1
Patent number: US08969352B2

Reaction notes

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