Sodium Carbonate → N-[(7-phenyl-9,9a-dihydro-3-oxo-1H,3H-oxazolo[3,4-a]indol-1-yl)methyl]acetamide

HRID 484409

Reaction equation

HRID 484409 reaction equation
Br[C:2]1[CH:10]=[CH:9][C:8]2[N:7]3[C:11](=[O:19])[O:12][CH:13]([CH2:14][NH:15][C:16](=[O:18])[CH3:17])[CH:6]3[CH2:5][C:4]=2[CH:3]=1.[C:20]1(B(O)O)[CH:25]=[CH:24][CH:23]=[CH:22][CH:21]=1.C(=O)([O-])[O-].[Na+].[Na+]>O1CCCC1.C(Cl)Cl.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.[Pd]>[C:20]1([C:2]2[CH:10]=[CH:9][C:8]3[N:7]4[C:11](=[O:19])[O:12][CH:13]([CH2:14][NH:15][C:16](=[O:18])[CH3:17])[CH:6]4[CH2:5][C:4]=3[CH:3]=2)[CH:25]=[CH:24][CH:23]=[CH:22][CH:21]=1

Participants

7

Reactant 3

HCID 10340Sodium CarbonateHCID 66827Phenylboronic AcidHCID 19795216N-[(7-bromo-9,9a-dihydro-3-oxo-1H,3H-oxazolo[3,4-a]indol-1-yl)methyl]acetamide

Product 1

HCID 54251491N-[(7-phenyl-9,9a-dihydro-3-oxo-1H,3H-oxazolo[3,4-a]indol-1-yl)methyl]acetamide

Reagents, catalysts & solvents 3

HCID 11979704Tetrakis(triphenylphosphine)palladiumCatalystHCID 6344DichloromethaneSolventHCID 8028TetrahydrofuranSolvent

Procedure

(±) (1S,9aS/1R,9aR) N-[(7-Bromo-9,9a-dihydro-3-oxo-1H,3H-oxazolo[3,4-a]indol-1-yl)methyl]acetamide (EXAMPLE 24, 129 mg) is dissolved in tetrahydrofuran (1 ml). To this mixture palladium tetrakis(triphenylphosphine) (22 mg), phenylboronic acid (61 mg) and aqueous sodium carbonate (2M, 0.45 ml) is added. The mixture is warmed for 15.5 hours in an oil bath at 68°. The mixture is then partitioned between aqueous sodium carbonate (2M, 2 ml) and methylene chloride (3 ml). After separation of the layers, the aqueous phase is extracted with additional methylene chloride (3×2 ml). The organic layers are combined, dried over magnesium sulfate and concentrated to provide a solid. This solid is taken up in methylene chloride and placed on a 20.5 cm×2.5 cm, 40-63μ silica column and eluted with ethyl acetate/methanol gradient. The appropriate fractions are pooled and concentrated to give the title compound, mp 181°-183°; NMR (CDCl3, 300 MHz) 7.43, 6.08, 4.53, 4.54, 3.83, 3.70, 3.35, 3.17 and 2.07 δ.

Workup

  1. temperatureThe mixture is warmed for 15.5 hours in an oil bath at 68°
  2. customThe mixture is then partitioned between aqueous sodium carbonate (2M, 2 ml) and methylene chloride (3 ml)
  3. customAfter separation of the layers
  4. extractionthe aqueous phase is extracted with additional methylene chloride (3×2 ml)
  5. dry with materialdried over magnesium sulfate
  6. concentrationconcentrated
  7. customto provide a solid
  8. washeluted with ethyl acetate/methanol gradient
  9. concentrationconcentrated

Sources & evidence

ORD record
ord-4d7c71f5970847059598c68effe37ed0
Source dataset
uspto-grants-1993_07
Patent number
US05231188

Linked notes

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