Methanol → 2-(2-((3-Nitrobenzyl)carbamoyl)-4-cyano-5-fluorophenoxy)acetic acid

HRID 2229572Notes

Reaction equation

HRID 2229572 reaction equation
C(C1C(F)=CC(O)=C(C=1)C(NCC1C=CC=C([N+]([O-])=O)C=1)=O)#N.C([O:26][C:27](=[O:52])[CH2:28][O:29][C:30]1[CH:35]=[C:34]([F:36])[C:33]([C:37]#[N:38])=[CH:32][C:31]=1[C:39](=[O:51])[NH:40][CH2:41][C:42]1[CH:47]=[CH:46][CH:45]=[C:44]([N+:48]([O-:50])=[O:49])[CH:43]=1)C.CO>O1CCOCC1.ClCCl>[C:37]([C:33]1[C:34]([F:36])=[CH:35][C:30]([O:29][CH2:28][C:27]([OH:52])=[O:26])=[C:31]([C:39](=[O:51])[NH:40][CH2:41][C:42]2[CH:47]=[CH:46][CH:45]=[C:44]([N+:48]([O-:50])=[O:49])[CH:43]=2)[CH:32]=1)#[N:38]

Participants

6

Reactant 3

HCID 887MethanolHCID 184681525-cyano-4-fluoro-2-hydroxy-N-(3-nitro-benzyl)-benzamideHCID 69453025[4-Cyano-5-fluoro-2-(3-nitro-benzylcarbamoyl)-phenoxy]-acetic acid ethyl ester

Product 1

HCID 184681662-(2-((3-Nitrobenzyl)carbamoyl)-4-cyano-5-fluorophenoxy)acetic acid

Reagents, catalysts & solvents 2

HCID 6344DichloromethaneSolventHCID 312751,4-DioxaneSolvent

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 6 methanol in dichloromethane); 1H NMR (DMSO-d6, 300 MHz) δ 9.12 (t, J=6.0 Hz, 1H), 8.21 (d, J=7.8 Hz, 1H), 8.19 (s, 1H), 8.10 (dd, J1=8.4 Hz, J2=2.6 Hz, 1H), 7.80 (d, J=8.4 Hz, 1H), 7.61 (t, J=8.0 Hz, 1H), 7.45 (d, J=11.4 Hz, 1H), 4.99 (s, 2H), 4.61 (d, J=6.0 Hz, 2H); 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

  1. customquenched after 15 minutes
  2. customhydrolysis of the cyano functionality

Sources & evidence

ORD record
ord-bec29fc11ea84c0896e0015544a1f0cd
Source dataset
uspto-grants-2002_07
Patent number
US06420426B1

Reaction notes

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