4-Chlorophenyl Isocyanate → (4-Chlorophenylaminocarbonyl)-6-hydroxy-1,2,3,4-tetrahydroisoquinoline-3-carboxylic acid

HRID 1432549Notes

Reaction equation

HRID 1432549 reaction equation
[OH:1][C:2]1[CH:3]=[C:4]2[C:9](=[CH:10][CH:11]=1)[CH2:8][NH:7][CH:6]([C:12]([OH:14])=[O:13])[CH2:5]2.[Cl:15][C:16]1[CH:21]=[CH:20][C:19]([N:22]=[C:23]=[O:24])=[CH:18][CH:17]=1>CN(C=O)C>[Cl:15][C:16]1[CH:21]=[CH:20][C:19]([NH:22][C:23]([CH:8]2[C:9]3[C:4](=[CH:3][C:2]([OH:1])=[CH:11][CH:10]=3)[CH2:5][CH:6]([C:12]([OH:14])=[O:13])[NH:7]2)=[O:24])=[CH:18][CH:17]=1

Participants

4

Reactant 2

HCID 76934-Chlorophenyl IsocyanateHCID 27331741,2,3,4-Tetrahydro-6-hydroxy-3-isoquinolinecarboxylic acid

Product 1

HCID 131727717(4-Chlorophenylaminocarbonyl)-6-hydroxy-1,2,3,4-tetrahydroisoquinoline-3-carboxylic acidYield 93.6%

Reagents, catalysts & solvents 1

HCID 6228DimethylformamideSolvent

Procedure

To a suspension of (D,L) 6-hydroxy-1,2,3,4-tetrahydroisoquinoline-3-carboxylic acid (500 mg, 2.59 mmol) in DMF (12 mL), 4-chlorophenyl isocyanate (400 mg, 2.60 mmol) was added. The reaction mixture was stirred at room temperature overnight, and the suspension became clear solution. It was then concentrated in vacuo. The residue was dissolved in CH2Cl2, and the product was extracted with 5N NaOH. The alkaline solution was then separated, acidified with 4N HCl to pH 2-3. The cloudy mixture was extracted with EtOAc. The EtOAc solution was dried over Na2SO4, concentrated in vacuo to give the titled compound as a solid (841 mg), which was pure enough for the next reaction.

Workup

  1. additionwas added
  2. concentrationIt was then concentrated in vacuo
  3. dissolutionThe residue was dissolved in CH2Cl2
  4. extractionthe product was extracted with 5N NaOH
  5. customThe alkaline solution was then separated
  6. extractionThe cloudy mixture was extracted with EtOAc
  7. dry with materialThe EtOAc solution was dried over Na2SO4
  8. concentrationconcentrated in vacuo

Sources & evidence

ORD record
ord-41e7c08d67f94928a3dc358a1e26e75a
Source dataset
uspto-grants-2009_11
Patent number
US07612089B2

Reaction notes

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