Potassium Carbonate → HCID 56597422, compound

HRID 2036198Notes

Reaction equation

HRID 2036198 reaction equation
C([O:3][C:4](=[O:9])[CH2:5][CH2:6][CH2:7]Br)C.[CH2:10]([O:17][C:18]([N:20]1[CH2:29][CH2:28][C:27]2[C:22](=[CH:23][CH:24]=[CH:25][CH:26]=2)[CH:21]1[C:30]1[CH:35]=[C:34]([F:36])[CH:33]=[CH:32][C:31]=1[OH:37])=[O:19])[C:11]1[CH:16]=[CH:15][CH:14]=[CH:13][CH:12]=1.C([O-])([O-])=O.[K+].[K+]>CN(C=O)C.CCOC(C)=O.O>[CH2:10]([O:17][C:18]([N:20]1[CH2:29][CH2:28][C:27]2[C:22](=[CH:23][CH:24]=[CH:25][CH:26]=2)[CH:21]1[C:30]1[CH:35]=[C:34]([F:36])[CH:33]=[CH:32][C:31]=1[O:37][CH2:7][CH2:6][CH2:5][C:4]([OH:9])=[O:3])=[O:19])[C:11]1[CH:16]=[CH:15][CH:14]=[CH:13][CH:12]=1

Participants

7

Reactant 3

HCID 11430Potassium CarbonateHCID 76300Ethyl 4-bromobutyrate2×HCID 66653803HCID 66653803, compound

Product 1

HCID 56597422HCID 56597422, compound

Reagents, catalysts & solvents 3

HCID 962WaterSolventHCID 6228DimethylformamideSolventHCID 8857Ethyl AcetateSolvent

Procedure

Ethyl-4-bromobutyrate (45 μL, 0.30 mmol, 1.50 eq.) was added to a solution of (±)-1-(5-fluoro-2-hydroxy-phenyl)-3,4-dihydro-1H-isoquinoline-2-carboxylic acid benzyl ester (75 mg, 0.20 mmol, 1.00 eq.) and K2CO3 (83 mg, 0.60 mmol) in DMF (0.7 mL). The mixture was stirred at r.t. for 2 hours. Ethyl-4-bromobutyrate (22 μL, 0.15 mmol, 0.75 eq.) was added again and the mixture was stirred at r.t. for 18 hours. The reaction mixture was diluted with AcOEt and water. The layers were separated and the aq. phase was extracted with AcOEt (2×). The combined org. phases were washed with water and sat. aq. NaCl soln., dried over MgSO4, filtered and concentrated in vacuo. To a solution of the crude ester in THF (0.9 mL), 1M aq. NaOH soln. (0.50 mL) was added. The resulting solution was stirred at r.t. during 62 hours. The org. solvent was removed in vacuo. The residue was diluted with water and 1M aq. HCl soln. (0.8 mL) followed by DCM. The mixture was shaked then the layers were separated and the aq. phase was extracted with DCM (2×). The comb. org. phases were dried over MgSO4, filtered and concentrated in vacuo. The crude mixture, redissolved in DMF (1.2 mL), was purified by prep. HPLC (column: Atlantis, 19×50 mm, 5 um, UV/MS, acidic conditions) and evaporated (genevac) to give the desired acid.

Workup

  1. stirringthe mixture was stirred at r.t. for 18 hours
  2. customThe layers were separated
  3. extractionthe aq. phase was extracted with AcOEt (2×)
  4. washphases were washed with water and sat. aq. NaCl soln
  5. dry with material, dried over MgSO4
  6. filtrationfiltered
  7. concentrationconcentrated in vacuo
  8. addition(0.50 mL) was added
  9. stirringThe resulting solution was stirred at r.t. during 62 hours
  10. customsolvent was removed in vacuo
  11. additionThe residue was diluted with water and 1M aq. HCl soln
  12. customthe layers were separated
  13. extractionthe aq. phase was extracted with DCM (2×)
  14. dry with materialphases were dried over MgSO4
  15. filtrationfiltered
  16. concentrationconcentrated in vacuo
  17. dissolutionThe crude mixture, redissolved in DMF (1.2 mL)
  18. customwas purified by prep
  19. customHPLC (column: Atlantis, 19×50 mm, 5 um, UV/MS, acidic conditions) and evaporated (genevac)

Sources & evidence

ORD record
ord-4baf70ef0bfa4288b0092bec13bdf98c
Source dataset
uspto-grants-2013_11
Patent number
US08575158B2

Reaction notes

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