Benzoic Acid → HCID 67848917, compound

HRID 487183Notes

Reaction equation

HRID 487183 reaction equation
Cl[C:2]1[CH:7]=[CH:6]C=C[C:3]=1[CH2:8][NH:9][C:10]1[C:18]([N+:19]([O-])=O)=[CH:17][CH:16]=[CH:15][C:11]=1[C:12](O)=O.[C:22]([Cl:28])(=O)[CH2:23][CH2:24][CH2:25][CH3:26].[C:29](O)(=O)C1C=CC=CC=1.[C:38](=[O:41])(O)[O-:39].[Na+].S(S([O-])=O)([O-])=O.[Na+].[Na+]>N1C=CC=CC=1.O1CCCC1>[CH2:3]([C:8]1[N:19]([C:23]2[CH:24]=[CH:25][CH:26]=[CH:29][C:22]=2[Cl:28])[C:18]2[C:17]([C:38]([OH:39])=[O:41])=[CH:16][CH:15]=[C:11]([CH3:12])[C:10]=2[N:9]=1)[CH2:2][CH2:7][CH3:6]

Participants

8

Reactant 5

HCID 243Benzoic AcidHCID 24489Sodium DithioniteHCID 61186Valeryl chlorideHCID 516892Sodium Bicarbonate2×HCID 19094224HCID 19094224, compound

Product 1

HCID 67848917HCID 67848917, compound

Reagents, catalysts & solvents 2

HCID 1049PyridineSolventHCID 8028TetrahydrofuranSolvent

Procedure

A solution of 2-[(2-chlorophenyl)-methyl]amino-3-nitrobenzoic acid (15.62 g, 0.051 mol) in pyridine (125 mL) was stirred with valeryl chloride (15.37 g, 0.127 mol) at 52° C. for 18 hours under argon. The usual workup gave the crude 2-[(2-chlorophenyl)methyl-N-valeryl]-amino-3-nitrobenzoic acid which was not purified. This benzoic acid (51 mmol) was dissolved in tetrahydrofuran (250 mL) and 5% sodium bicarbonate solution (250 mL) was added to give a pH of 7.41. Sodium hydrosulfite (7 times 15 g portions) was added over 3 hours with the pH being adjusted to 7.1 with solid sodium bicarbonate. The mixture was filtered, some ether was added and the organic layer was washed with brine, stirred over magnesium sulfate, filtered and concentrated to a slurry. This crude aminobenzoic acid (23.9 g) was dissolved in a mixture of acetic acid (120 mL) and concentrated hydrochloric acid (40 mL) and heated on a steam bath for 1.5 hours. The solvents were removed in vacuo, and ice water was added to the residue. The precipitated crystals were filtered, washed with water and dried to provide 12.04 g of crude product. Crystallization from methanol gave 9.1 g of 2-n-butyl-1-(2-chlorophenyl)-methyl-1H-benzimidazole-7-carboxylic acid; mp 253°-255° C.

Workup

  1. customThe usual workup gave the crude 2-[(2-chlorophenyl)methyl-N-valeryl]-amino-3-nitrobenzoic acid which
  2. customwas not purified
  3. customto give a pH of 7.41
  4. filtrationThe mixture was filtered
  5. additionsome ether was added
  6. washthe organic layer was washed with brine
  7. filtrationfiltered
  8. concentrationconcentrated to a slurry
  9. dissolutionThis crude aminobenzoic acid (23.9 g) was dissolved in a mixture of acetic acid (120 mL) and concentrated hydrochloric acid (40 mL)
  10. temperatureheated on a steam bath for 1.5 hours
  11. customThe solvents were removed in vacuo, and ice water
  12. additionwas added to the residue
  13. filtrationThe precipitated crystals were filtered
  14. washwashed with water
  15. customdried
  16. customto provide 12.04 g of crude product
  17. customCrystallization from methanol

Sources & evidence

ORD record
ord-00d674fdd9814c54a96f8951139634ae
Source dataset
uspto-grants-1994_03
Patent number
US05294631

Reaction notes

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