Methanol → 2-(2-((3-Nitrobenzyl)carbamoyl)-4-cyano-5-fluorophenoxy)acetic acid
Reaction equation
C([O:3][C:4](=[O:29])[CH2:5][O:6][C:7]1[CH:12]=[C:11]([F:13])[C:10]([C:14]#[N:15])=[CH:9][C:8]=1[C:16](=[O:28])[NH:17][CH2:18][C:19]1[CH:24]=[CH:23][CH:22]=[C:21]([N+:25]([O-:27])=[O:26])[CH:20]=1)C.CO>O1CCOCC1.ClCCl>[C:14]([C:10]1[C:11]([F:13])=[CH:12][C:7]([O:6][CH2:5][C:4]([OH:29])=[O:3])=[C:8]([C:16](=[O:28])[NH:17][CH2:18][C:19]2[CH:24]=[CH:23][CH:22]=[C:21]([N+:25]([O-:27])=[O:26])[CH:20]=2)[CH:9]=1)#[N:15]Participants
Procedure
[4-Cyano-5-fluoro-2-(3-nitro-benzylcarbamoyl)-phenoxy]-acetic acid was prepared in an analogous manner to that set forth in Example 45 (Steps 8–9) except that in Step 8,5-cyano-4-fluoro-2-hydroxy-N-(3-nitro-benzyl)-benzamide was used in place of N-(4-bromo-2-fluorobenzyl)-4-fluoro-2-hydroxy-5-methyl-benzamide. In Step 9, special care was taken in the hydrolysis of [4-cyano-5-fluoro-2-(3-nitro-benzylcarbamoyl)-phenoxy]-acetic acid ethyl ester. The hydrolysis was performed in dioxane instead of ethanol and quenched after 15 minutes to prevent hydrolysis of the cyano functionality: mp 179–180° C.; Rf 0.22 (20% methanol in dichloromethane); 1H NMR (DMSO-d6, 300 MHz) δ 9.12 (t, J=6.0 Hz, 1 H), 8.21 (d, J=7.8 Hz, 1 H), 8.19 (s, 1 H), 8.10 (dd, J, =8.4 Hz, J2=2.6 Hz, 1 H), 7.80 (d, J=8.4 Hz, 1 H), 7.61 (t, J=8.0 Hz, 1 H), 7.45 (d, J=11.4 Hz, 1 H), 4.99 (s, 2 H), 4.61 (d, J=6.0 Hz, 2 H); ESI-LC/MS m/z calcd for C17H12FN3O6: 373.1; Found 472.0 (M−1)−. Anal. calcd for C17H12FN3O6: C, 54.70; N, 11.26; H, 3.24. Found C, 54.43; N, 11.07; H, 3.32.
Workup
- customquenched after 15 minutes
- customhydrolysis of the cyano functionality
Sources & evidence
- ORD record
- ord-a93433e98c104dbfb3edaf4d71bbeb5e
- Source dataset
- uspto-grants-2007_03
- Patent number
- US07189749B2
Reaction notes
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