Ethyl bromoacetate → HCID 66653982, compound

HRID 2036204Notes

Reaction equation

HRID 2036204 reaction equation
C(OC([N:11]1[CH2:20][CH2:19][C:18]2[C:13](=[CH:14][CH:15]=[C:16]([F:21])[CH:17]=2)[CH:12]1[C:22]1[CH:27]=[C:26]([Cl:28])[CH:25]=[CH:24][C:23]=1[O:29][CH2:30]C=C)=O)C1C=CC=CC=1.CN1[C:41](=O)[CH2:40][C:38](=O)N(C)C1=O.[C:44](=[O:47])([O-])[O-:45].[K+].[K+].BrC[C:52]([O:54][CH2:55][CH3:56])=[O:53].[CH3:57][CH2:58]OC(C)=O>CO.CN(C=O)C.O.[Pd].C1(P(C2C=CC=CC=2)C2C=CC=CC=2)C=CC=CC=1.C1(P(C2C=CC=CC=2)C2C=CC=CC=2)C=CC=CC=1.C1(P(C2C=CC=CC=2)C2C=CC=CC=2)C=CC=CC=1.C1(P(C2C=CC=CC=2)C2C=CC=CC=2)C=CC=CC=1>[CH2:55]([O:54][C:52]([N:11]1[CH2:20][CH2:19][C:18]2[C:13](=[CH:14][CH:15]=[C:16]([F:21])[CH:17]=2)[CH:12]1[C:22]1[CH:27]=[C:26]([Cl:28])[CH:25]=[CH:24][C:23]=1[O:29][CH2:30][C:44]([OH:45])=[O:47])=[O:53])[C:56]1[CH:38]=[CH:40][CH:41]=[CH:58][CH:57]=1

Participants

10

Reactant 5

HCID 7748Ethyl bromoacetateHCID 8857Ethyl AcetateHCID 11430Potassium CarbonateHCID 69860Dimethylbarbituric acidHCID 66655882HCID 66655882, compound

Product 1

HCID 66653982HCID 66653982, compound

Reagents, catalysts & solvents 4

HCID 11979704Tetrakis(triphenylphosphine)palladiumCatalystHCID 887MethanolSolventHCID 962WaterSolventHCID 6228DimethylformamideSolvent

Procedure

A mixture under N2 of (±)-1-(2-allyloxy-5-chloro-phenyl)-6-fluoro-3,4-dihydro-1H-isoquinoline-2-carboxylic acid benzyl ester (65 mg, 0.14 mmol, 1.00 eq.), 1,3-dimethylbarbituric acid (45 mg, 0.29 mmol, 2.00 eq.) and tetrakis(triphenylphosphine) palladium (0) (8.3 mg, 0.007 mmol, 0.05 eq.) in MeOH (3 mL) was stirred at r.t. for 3 hours. The mixture was partitioned between AcOEt (15 mL) and water (15 mL). The layers were separated and the aq. phase was extracted with AcOEt (2×15 mL). The comb. org. phases were washed with sat. aq. NaCl soln. (1×15 mL), dried over MgSO4, filtered, and concentrated in vacuo. To a solution of the residue and potassium carbonate anhydrous (60 mg, 0.43 mmol, 3.0 eq.) in DMF (2 mL), ethyl bromoacetate (48 μL, 0.43 mmol, 3.0 eq.) was added. The reaction mixture was stirred at r.t. during 2 hours. The reaction mixture was diluted with water (15 mL) and AcOEt (30 mL). The layers were separated. The aq. phase was extracted with AcOEt (2×15 mL). The comb. org. phases were washed with water (1×15 mL), sat. aq. NaCl soln. (1×15 mL), dried over MgSO4, filtered, and concentrated in vacuo. To a solution of the residue in DMF (1.1 mL), 1M aq. NaOH (0.6 mL) was added. The resulting solution was stirred at r.t. for 24 hours. The solution was acidified with formic acid (0.6 mL). The crude product was purified by prep. HPLC (column: Atlantis, 30×75 mm, 10 um, UV/MS, acidic conditions) and evaporated to give the title compound.

Workup

  1. customThe mixture was partitioned between AcOEt (15 mL) and water (15 mL)
  2. customThe layers were separated
  3. extractionthe aq. phase was extracted with AcOEt (2×15 mL)
  4. washphases were washed with sat. aq. NaCl soln
  5. dry with material(1×15 mL), dried over MgSO4
  6. filtrationfiltered
  7. concentrationconcentrated in vacuo
  8. customThe layers were separated
  9. extractionThe aq. phase was extracted with AcOEt (2×15 mL)
  10. washphases were washed with water (1×15 mL), sat. aq. NaCl soln
  11. dry with material(1×15 mL), dried over MgSO4
  12. filtrationfiltered
  13. concentrationconcentrated in vacuo
  14. additionTo a solution of the residue in DMF (1.1 mL), 1M aq. NaOH (0.6 mL) was added
  15. stirringThe resulting solution was stirred at r.t. for 24 hours
  16. customThe crude product was purified by prep
  17. customHPLC (column: Atlantis, 30×75 mm, 10 um, UV/MS, acidic conditions) and evaporated

Sources & evidence

ORD record
ord-d4115c790eae4fdbb998264607998a09
Source dataset
uspto-grants-2013_11
Patent number
US08575158B2

Reaction notes

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