4-Aminobenzoic Acid → HCID 24785681, compound

HRID 2422922Notes

Reaction equation

HRID 2422922 reaction equation
[NH2:1][C:2]1[CH:10]=[CH:9][C:5]([C:6]([OH:8])=[O:7])=[CH:4][CH:3]=1.[OH-].[Na+].C([O-])([O-])=O.[Na+].[Na+].Cl[C:20]1[C:25](CC=O)=[C:24]([CH3:29])[CH:23]=[CH:22][C:21]=1[S:30]([O-:33])(=[O:32])=[O:31].C1C[O:37][CH2:36][CH2:35]1>O.C(OCC)C>[S:30]([O:33][CH2:35][C:36]([NH:1][C:2]1[CH:10]=[CH:9][C:5]([C:6]([OH:8])=[O:7])=[CH:4][CH:3]=1)=[O:37])([C:21]1[CH:20]=[CH:25][C:24]([CH3:29])=[CH:23][CH:22]=1)(=[O:31])=[O:32]

Participants

8

Reactant 5

HCID 9784-Aminobenzoic AcidHCID 8028TetrahydrofuranHCID 10340Sodium CarbonateHCID 14798Sodium HydroxideHCID 86628698HCID 86628698, compound

Product 1

HCID 24785681HCID 24785681, compoundYield 62%

Reagents, catalysts & solvents 2

HCID 962WaterSolventHCID 3283Diethyl EtherSolvent

Procedure

A mixture of p-aminobenzoic acid (92 mg, 0.67 mmol) and NaOH (27 mg, 0.67 mmol) in water (6 ml) was stirred at room temperature for 10 min until all of the solid material had dissolved. Na2CO3 (59 mg, 0.5561 mmol) was then added and the mixture cooled to 0° C. A solution of 2-chloro-2-oxoethyl-4-methylbenzenesulfonate (4, 200 mg, 0.8044 mmol) in THF (2 ml) was injected rapidly and the resulting solution allowed to warm to room temperature and stirred for 2 h. Then reaction mixture was poured into a separating funnel containing diethyl ether. The phases were separated and the aqueous phase washed with a further portion of diethyl ether. The aqueous phase was acidified to pH 1 by addition of 1N HCl solution and the product extracted into ethyl acetate. The ethyl acetate was washed twice with 1N HCl solution and the organic phase was dried (Na2SO4), filtered and the solvent removed in vacuo. The resulting pale orange solid was recrystallized from chloroform/MeOH (20:1) affording 5 as a white powder (146 mg, 62%). δH (400 MHz, DMSO) 2.37 (3H, s, Me), 4.70 (2H, s, CH2), 7.46 (2H, d, J=8 Hz, ArH), 7.59 (2H, d, J=8.6 Hz, ArH), 7.82 (2H, d, J=8 Hz, ArH), 7.87 (2H, d, J=8.6 Hz, ArH), 10.39 (1H, s, NH), 12.72 (1H, CO2H); δc (100.6 MHz, DMSO) 21.8, 68.0, 119.4, 126.4, 128.5, 130.9, 131.1, 132.7, 142.7, 146.0, 164.4, 167.5; MS (ES+) 349.7 (100%, [M+H]+), 371.7 (40%, [M+Na]+); MS (ES−) 347.9 (100%, [M−H]−); HRMS [M−H]− requires 348.05473, found 348.05334.

Workup

  1. dissolutionhad dissolved
  2. temperaturethe mixture cooled to 0° C
  3. temperatureto warm to room temperature
  4. stirringstirred for 2 h
  5. customThen reaction mixture
  6. additionwas poured into a separating funnel
  7. customThe phases were separated
  8. washthe aqueous phase washed with a further portion of diethyl ether
  9. additionThe aqueous phase was acidified to pH 1 by addition of 1N HCl solution
  10. extractionthe product extracted into ethyl acetate
  11. washThe ethyl acetate was washed twice with 1N HCl solution
  12. dry with materialthe organic phase was dried (Na2SO4)
  13. filtrationfiltered
  14. customthe solvent removed in vacuo
  15. customThe resulting pale orange solid was recrystallized from chloroform/MeOH (20:1)

Sources & evidence

ORD record
ord-c45c9e9200814fec83a0838228f5d1c8
Source dataset
uspto-grants-2011_06
Patent number
US07960434B2

Reaction notes

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