Phenol → HCID 90022830, compound

HRID 1754848Notes

Reaction equation

HRID 1754848 reaction equation
[C:1]([O:5][C:6]([N:8]1[CH2:13][CH2:12][C:11]2[N:14]=[CH:15][S:16][C:10]=2[CH:9]1[C:17]1[CH:22]=[C:21]([F:23])[CH:20]=[CH:19][C:18]=1[O:24][CH2:25]C=C)=[O:7])([CH3:4])([CH3:3])[CH3:2].CN1C(=O)CC(=O)N(C)C1=O.C1(O)C=CC=CC=1.C(=O)([O-])[O-].[K+].[K+].BrC[C:54]([O:56][CH2:57][CH3:58])=[O:55]>CO.CN(C=O)C.CCOC(C)=O.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>[C:1]([O:5][C:6]([N:8]1[CH2:13][CH2:12][C:11]2[N:14]=[CH:15][S:16][C:10]=2[CH:9]1[C:17]1[CH:22]=[C:21]([F:23])[CH:20]=[CH:19][C:18]=1[O:24][CH2:25][C:54]([O:56][CH2:57][CH3:58])=[O:55])=[O:7])([CH3:2])([CH3:4])[CH3:3]

Participants

11

Reactant 5

HCID 996PhenolHCID 7748Ethyl bromoacetate3×HCID 11430Potassium Carbonate2×HCID 69860Dimethylbarbituric acidHCID 90022313HCID 90022313, compound

Product 1

HCID 90022830HCID 90022830, compound

Reagents, catalysts & solvents 5

HCID 11979704Tetrakis(triphenylphosphine)palladiumCatalystHCID 887MethanolSolventHCID 962WaterSolventHCID 6228DimethylformamideSolventHCID 8857Ethyl AcetateSolvent

Procedure

A mixture under N2 of (±)-4-(2-allyloxy-5-fluoro-phenyl)-6,7-dihydro-4H-thiazolo[5,4-c]pyridine-5-carboxylic acid tert-butyl ester (261 mg, 0.61 mmol, 1.00 eq.), 1,3-dimethylbarbituric acid (191 mg, 1.21 mmol, 2.00 eq.) and tetrakis(triphenylphosphine) palladium (0) (35 mg, 30 μmol, 0.05 eq.) in MeOH (12 mL) was stirred at r.t. for 18 hours. The mixture was partitioned between AcOEt (55 mL) and water (55 mL). The layers were separated and the aq. phase was extracted with AcOEt (2×55 mL). The comb. org. phases were washed with sat. aq. NaCl soln. (1×55 mL), dried over MgSO4, and concentrated in vacuo. To a solution of the resulting crude phenol and potassium carbonate (252 mg, 1.82 mmol, 3.00 eq.) in DMF (2.1 mL), ethyl bromoacetate (0.1 mL, 0.91 mmol, 1.50 eq.) was added. The mixture was stirred at r.t. for 18 hours. Ethyl bromoacetate (50 μL, 0.46 mmol, 1.33 eq.) was added again and the mixture was stirred at r.t. for 7 hours. LC/MS still showed starting material. Ethyl bromoacetate (67 μL, 0.61 mmol, 1.00 eq.) and potassium carbonate (126 mg, 0.91 mmol, 1.50 eq.) were 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 comb. org. extracts were washed with water and sat. aq. NaCl soln., dried over MgSO4, filtered, and concentrated in vacuo. The residue was purified by flashmaster (column: 50 g, flow: 30 mL/min, 50 fractions of 30 mL, Heptane to Heptane+40% AcOEt) to yield the title compound as an orange oil.

Workup

  1. customThe mixture was partitioned between AcOEt (55 mL) and water (55 mL)
  2. customThe layers were separated
  3. extractionthe aq. phase was extracted with AcOEt (2×55 mL)
  4. washphases were washed with sat. aq. NaCl soln
  5. dry with material(1×55 mL), dried over MgSO4
  6. concentrationconcentrated in vacuo
  7. stirringthe mixture was stirred at r.t. for 7 hours
  8. stirringthe mixture was stirred at r.t. for 18 hours
  9. customThe layers were separated
  10. extractionthe aq. phase was extracted with AcOEt (2×)
  11. washextracts were washed with water and sat. aq. NaCl soln
  12. dry with material, dried over MgSO4
  13. filtrationfiltered
  14. concentrationconcentrated in vacuo
  15. customThe residue was purified by flashmaster (column: 50 g, flow: 30 mL/min, 50 fractions of 30 mL, Heptane to Heptane+40% AcOEt)

Sources & evidence

ORD record
ord-de372f34e7874302926dd5b6599d644a
Source dataset
uspto-grants-2015_10
Patent number
US09169270B2

Reaction notes

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