3-Amino-4-chlorobenzoic acid → HCID 67056869, compound

HRID 1921284Notes

Reaction equation

HRID 1921284 reaction equation
[NH2:1][C:2]1[CH:3]=[C:4]([CH:8]=[CH:9][C:10]=1[Cl:11])[C:5]([OH:7])=[O:6].C[Si](C)(C)[N-][Si](C)(C)C.[Li+].[F:22][C:23]1[CH:28]=[CH:27][CH:26]=[C:25]([F:29])[C:24]=1[N:30]1[C:35](=[O:36])[CH:34]=[CH:33][C:32]([C:37](Cl)=[O:38])=[CH:31]1>C1COCC1>[Cl:11][C:10]1[CH:9]=[CH:8][C:4]([C:5]([OH:7])=[O:6])=[CH:3][C:2]=1[NH:1][C:37]([C:32]1[CH:33]=[CH:34][C:35](=[O:36])[N:30]([C:24]2[C:25]([F:29])=[CH:26][CH:27]=[CH:28][C:23]=2[F:22])[CH:31]=1)=[O:38]

Participants

5

Reactant 3

HCID 760923-Amino-4-chlorobenzoic acidHCID 2733832Lithium HexamethyldisilazideHCID 86639848HCID 86639848, compound

Product 1

HCID 67056869HCID 67056869, compoundYield 24%

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent3×

Conditions

Temperature
-5 °C

Procedure

To a solution of 3-amino-4-chlorobenzoic acid (509 mg) in THF (8 mL) was added dropwise an 1 M THF solution of lithium 1,1,1,3,3,3-hexamethyldisilazan-2-ide (6 mL) while keeping the internal temperature below −5° C. under a nitrogen atmosphere, and the mixture was stirred around −5° C. for 30 min. To the solution was added dropwise a solution of 1-(2,6-difluorophenyl)-6-oxo-1,6-dihydro-3-pyridinecarbonyl chloride (800 mg) in THF (8 ml), and the resulting mixture was stirred around −5° C. for 1 hr. The reaction mixture was partitioned between EtOAc (16 mL) and 1 M HCl (16 mL). The aqueous layer was extracted with EtOAc (8 mL). The organic layers were combined, washed with brine two times, dried over MgSO4, filtered and evaporated in vacuo. The residue was triturated with CH2Cl2, and the precipitates produced were collected by filtration. The isolated product was triturated with MeOH and collected by filtration to give 4-chloro-3-({[1-(2,6-difluorophenyl)-6-oxo-1,6-dihydro-3-pyridinyl]carbonyl}amino)benzoic acid (288 mg).

Workup

  1. customthe internal temperature below −5° C.
  2. stirringthe resulting mixture was stirred around −5° C. for 1 hr
  3. customThe reaction mixture was partitioned between EtOAc (16 mL) and 1 M HCl (16 mL)
  4. extractionThe aqueous layer was extracted with EtOAc (8 mL)
  5. washwashed with brine two times
  6. dry with materialdried over MgSO4
  7. filtrationfiltered
  8. customevaporated in vacuo
  9. customThe residue was triturated with CH2Cl2
  10. customthe precipitates produced
  11. filtrationwere collected by filtration
  12. customThe isolated product was triturated with MeOH
  13. filtrationcollected by filtration

Sources & evidence

ORD record
ord-04bc4de6acb6419f8044c8dd1efa7431
Source dataset
uspto-grants-2012_05
Patent number
US08173684B2

Reaction notes

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