Dimethylbarbituric acid → Isoindoline

HRID 2036228Notes

Reaction equation

HRID 2036228 reaction equation
C(OC([N:8]1[CH2:16][C:15]2[C:10](=[CH:11][CH:12]=[CH:13][CH:14]=2)[CH:9]1C1C=C(Cl)C=CC=1OCC=C)=O)(C)(C)C.CN1C(=O)CC(=O)N(C)C1=O>CO.[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>[CH2:9]1[C:10]2[C:15](=[CH:14][CH:13]=[CH:12][CH:11]=2)[CH2:16][NH:8]1

Participants

5

Reactant 2

HCID 69860Dimethylbarbituric acidHCID 66654099HCID 66654099, compound

Product 1

HCID 422478Isoindoline

Reagents, catalysts & solvents 2

HCID 11979704Tetrakis(triphenylphosphine)palladiumCatalystHCID 887MethanolSolvent

Procedure

A mixture under N2 of (±)-1-(2-allyloxy-5-chloro-phenyl)-1,3-dihydro-isoindole-2-carboxylic acid tert-butyl ester (10.35 g, 26.8 mmol, 1.00 eq.), 1,3-dimethylbarbituric acid (8.38 g, 53.6 mmol, 2.00 eq.) and tetrakis(triphenylphosphine) palladium (0) (1.55 g, 1.34 mmol, 0.05 eq.) in MeOH (300 mL) was stirred at r.t. for 5 hours. The mixture was partitioned between AcOEt (250 mL) and water (250 mL). The layers were separated and the aq. phase was extracted with AcOEt (2×100 mL). The comb. org. phases were washed with sat. aq. NaCl soln. (1×250 mL), dried over MgSO4, and concentrated in vacuo. The residue was purified by flash master (column: 340 g, flow: 90 mL/min, Heptane to Heptane+50% AcOEt) to give the desired phenol 30.

Workup

  1. customThe mixture was partitioned between AcOEt (250 mL) and water (250 mL)
  2. customThe layers were separated
  3. extractionthe aq. phase was extracted with AcOEt (2×100 mL)
  4. washphases were washed with sat. aq. NaCl soln
  5. dry with material(1×250 mL), dried over MgSO4
  6. concentrationconcentrated in vacuo
  7. customThe residue was purified by flash master (column: 340 g, flow: 90 mL/min, Heptane to Heptane+50% AcOEt)

Sources & evidence

ORD record
ord-fb3ac31e0b32420fb3959a48fb6f4dc0
Source dataset
uspto-grants-2013_11
Patent number
US08575158B2

Reaction notes

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