Sodium Hydroxide → 4-{[3-chloro-4-[(2,4-difluorobenzyl)oxy]-6-methyl-2-oxopyridin-1(2H)-yl]methyl}benzoic acid

HRID 1867127Notes

Reaction equation

C[O:2][C:3](=[O:30])[C:4]1[CH:9]=[CH:8][C:7]([CH2:10][N:11]2[C:16]([CH3:17])=[CH:15][C:14]([O:18][CH2:19][C:20]3[CH:25]=[CH:24][C:23]([F:26])=[CH:22][C:21]=3[F:27])=[C:13]([Cl:28])[C:12]2=[O:29])=[CH:6][CH:5]=1.[OH-].[Na+]>CO.O1CCOCC1>[Cl:28][C:13]1[C:12](=[O:29])[N:11]([CH2:10][C:7]2[CH:6]=[CH:5][C:4]([C:3]([OH:30])=[O:2])=[CH:9][CH:8]=2)[C:16]([CH3:17])=[CH:15][C:14]=1[O:18][CH2:19][C:20]1[CH:25]=[CH:24][C:23]([F:26])=[CH:22][C:21]=1[F:27]

Participants

Conditions

Temperature: 50 °C

Procedure

Methyl-4-{[3-chloro-4-[(2,4-difluorobenzyl)oxy]-6-methyl-2-oxopyridin-1(2H)-yl]methyl}benzoate (30.4 g, 70.1 mmol) was suspended in methanol (150 mL) and dioxane (150 mL). 2.5N NaOH (30.8 mL, 77.08 mmol) was added. The resulting mixture was heated to 50° C. for 8.0 hours. The reaction was partially concentrated and the heterogenous mixture was acidified (pH 2) with 1N Hcl. The precipitate was collected by filtration washing with H2O and diethyl ether to afford a white solid (29.2 g, 99%). 1H NMR (400 MHz, DMSO-d6) δ 7.88 (d, J=8.3 Hz, 2H), 7.63 (app q, J=7.9 Hz, 1H), 7.31 (dt, J=2.4, 9.9 Hz, 1H), 7.18 (app d, J=8.3 Hz, 2H), 7.17-7.12 (m, 1H), 6.60 (s, 1H), 5.35 (s, 2H), 5.27 (s, 2H), 2.28 (s, 3H). ES-HRMS m/z 420.0821 (M+H calcd for C21H17ClF2NO4 requires 420.0809).

Workup

concentrationThe reaction was partially concentrated
filtrationThe precipitate was collected by filtration
washwashing with H2O and diethyl ether

Sources & evidence

ORD record: ord-0911103dc59747d288c894b044d00695
Source dataset: uspto-grants-2009_12
DOI: 10.6084/m9.figshare.5104873.v1
Patent number: US07629363B2

Reaction notes

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