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

HRID 1928568Notes

Reaction equation

HRID 1928568 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>[CH3:1][O:12][C:11](=[O:13])[C:10]1[CH:14]=[C:15]([N+:16]([O-:18])=[O:17])[C:7]([NH2:6])=[C:8]([F:20])[C:9]=1[F:19]

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 (132.3 g, 0.607 mol, 1 equiv.) in 325 mL of MeOH. The mixture was heated at reflux for 15 hours. When the reaction was complete as determined by HPLC, the mixture was cooled in an ice-water bath for 45 minutes. The reaction mixture was then filtered and the cake was washed with 65 mL of MeOH. The wet cake was dried overnight at 55° C. under high vacuum to give 128.8 g (92%) of 4-amino-2,3-difluoro-5-nitrobenzoic acid methyl ester. HPLC was 97.9a % (220 nm) and 99.2a % (254 nm). 1H NMR (400 MHz, DMSO-d6) 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, DMSO-d6) 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 mixture was cooled in an ice-water bath for 45 minutes
  4. filtrationThe reaction mixture was then 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-d4a4241e47764360806b5dc3701d4c54
Source dataset
uspto-grants-2012_05
Patent number
US08183385B2

Reaction notes

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