Triethylamine → HCID 89648585, compound

HRID 1773989Notes

Reaction equation

HRID 1773989 reaction equation
[CH2:1]([O:8][C:9]([N:11]1[CH2:20][CH2:19][C:18]2[C:13](=[C:14]([C:21]3[CH:26]=[C:25]([F:27])[CH:24]=[CH:23][C:22]=3[O:28]CC3C=CC=CC=3)[CH:15]=[CH:16][CH:17]=2)[CH2:12]1)=[O:10])[C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][CH:3]=1.C(N(CC)CC)C.ClC(OCC1C=CC=CC=1)=O>CCO.[Pd].C(Cl)Cl>[CH2:1]([O:8][C:9]([N:11]1[CH2:20][CH2:19][C:18]2[C:13](=[C:14]([C:21]3[CH:26]=[C:25]([F:27])[CH:24]=[CH:23][C:22]=3[OH:28])[CH:15]=[CH:16][CH:17]=2)[CH2:12]1)=[O:10])[C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][CH:3]=1

Participants

7

Reactant 3

HCID 8471TriethylamineHCID 10387Benzyl chloroformateHCID 89648496HCID 89648496, compound

Product 1

HCID 89648585HCID 89648585, compound

Reagents, catalysts & solvents 3

HCID 23938PalladiumCatalystHCID 702EthanolSolventHCID 6344DichloromethaneSolvent

Procedure

To a solution under N2 of 8-(2-benzyloxy-5-fluoro-phenyl)-3,4-dihydro-1H-isoquinoline-2-carboxylic acid benzyl ester (208 mg, 0.45 mmol, 1.0 eq.) in EtOH (10 mL), palladium on activated carbon (10 wt. %, 21 mg) was added. The flask was evacuated and refilled with H2. The black suspension was stirred at r.t. under an H2-atmosphere for 6 hours. The black suspension was filtered through Celite and the filtrate was concentrated in vacuo to give a beige foam. To an-ice cooled suspension of the residue and triethylamine (93 μL, 0.67 mmol, 1.5 eq.) in DCM (10 mL), benzyl chloroformate (67 μL, 0.45 mmol, 1.0 eq.) was added dropwise. Upon completion of the addition, the mixture was stirred at 0° C. for 1 hour and further at r.t. for 4 hours. The reaction was quenched with 1M aq. citric acid soln. (10 mL). The layers were separated. The aq. phase was extracted with DCM (3×10 mL). The comb. org. phases were dried over Na2SO4 and concentrated in vacuo. The residue was dissolved in THF (10 mL) and 1M aq. NaOH (2 mL) was added. The mixture was stirred at r.t. for 64 hours. The org. solvent was removed in vacuo and the aq. layer was acidified with 2N aq. HCl. The aq. layer was extracted with DCM (3×10 mL). The comb. org. phases were dried over MgSO4 and concentrated in vacuo. The residue was purified by CC (SiO2, Hept/AcOEt 7:3) to give the title compound as a white foam.

Workup

  1. customThe flask was evacuated
  2. additionrefilled with H2
  3. filtrationThe black suspension was filtered through Celite
  4. concentrationthe filtrate was concentrated in vacuo
  5. customto give a beige foam
  6. temperatureTo an-ice cooled
  7. additionwas added dropwise
  8. additionUpon completion of the addition
  9. stirringthe mixture was stirred at 0° C. for 1 hour and further at r.t. for 4 hours
  10. customThe reaction was quenched with 1M aq. citric acid soln
  11. customThe layers were separated
  12. extractionThe aq. phase was extracted with DCM (3×10 mL)
  13. dry with materialphases were dried over Na2SO4
  14. concentrationconcentrated in vacuo
  15. dissolutionThe residue was dissolved in THF (10 mL)
  16. addition1M aq. NaOH (2 mL) was added
  17. stirringThe mixture was stirred at r.t. for 64 hours
  18. customsolvent was removed in vacuo
  19. extractionThe aq. layer was extracted with DCM (3×10 mL)
  20. dry with materialphases were dried over MgSO4
  21. concentrationconcentrated in vacuo
  22. customThe residue was purified by CC (SiO2, Hept/AcOEt 7:3)

Sources & evidence

ORD record
ord-59b8881eeb5249329722efd393a93756
Source dataset
uspto-grants-2016_02
Patent number
US09255090B2

Reaction notes

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