Chlorotrimethylsilane → Benzoic acid, 4-amino-2,3-difluoro-5-nitro-, methyl ester

HRID 1665845Notes

Reaction equation

HRID 1665845 reaction equation
[CH3:1][Si](Cl)(C)C.[NH2:6][C:7]1[C:15]([N+:16]([O-:18])=[O:17])=[CH:14][C:10]([C:11]([OH:13])=[O:12])=[C:9]([F:19])[C:8]=1[F:20]>CO>[NH2:6][C:7]1[C:15]([N+:16]([O-:18])=[O:17])=[CH:14][C:10]([C:11]([O:13][CH3:1])=[O:12])=[C:9]([F:19])[C:8]=1[F:20]

Participants

4

Reactant 2

HCID 6397ChlorotrimethylsilaneHCID 162440884-Amino-2,3-difluoro-5-nitrobenzoic acid

Product 1

HCID 2759749Benzoic acid, 4-amino-2,3-difluoro-5-nitro-, methyl esterYield 92%

Reagents, catalysts & solvents 1

HCID 887MethanolSolvent

Procedure

TMSCl (132 g, 1.21 mol, 2.0 equiv) was added over 5 minutes to a slurry of 4-amino-2,3-difluoro-5-nitrobenzoic acid (3) (132.3 g, 0.607 mol, 1 equiv) in 325 mL of MeOH. The mixture was heated at reflux for 15 hours. Once the reaction was complete by HPLC, the reaction mixture was cooled in an ice-water bath for 45 minutes. Then the reaction mixture was filtered and the cake was washed with 65 mL of MeOH. The wet cake was dried overnight at 55° C. under high vacuum to provide 128.8 g (92%) of 4-amino-2,3-difluoro-5-nitrobenzoic acid methyl ester (4). HPLC was 97.9 a % (220 nm) and 99.2 a % (254 nm). 1H NMR (400 MHz, d6 DMSO) δ 3.84 (3H, s, OMe), 8.1 (2H, br s, NH2), 8.43 (1H, apparent dd, J 1.9, 7.2, Ar—H). 19F NMR (376 MHz, d6 DMSO) δ −153.6, −129.2. 13C NMR (100 MHz, d6 DMSO) δ 52 (CH3O), 105 (C, d, J 10), 125 (CH, t, J 2.7,), 128 (CH, d, J 5), 140 (C—F, dd, J 244, 15,), 141 (C, dd, J 14, 5), 152 (C—F, dd, J 263, 11), 162 (COO, t, J 3). IR νmax/cm−1 3433, 3322, 1699, 1637, 1548, 1342, 1234. MS APCI (−) m/z 231 (M−1) detected.

Workup

  1. temperatureThe mixture was heated
  2. temperatureat reflux for 15 hours
  3. temperaturethe reaction mixture was cooled in an ice-water bath for 45 minutes
  4. filtrationThen the reaction mixture was filtered
  5. washthe cake was washed with 65 mL of MeOH
  6. customThe wet cake was dried overnight at 55° C. under high vacuum

Sources & evidence

ORD record
ord-c0c77f57b358437da73b1362a73c56d8
Source dataset
uspto-grants-2011_10
Patent number
US08039637B2

Reaction notes

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