Sodium Carbonate → 6,6-Dimethyl-3-phenyl-1-(pyridin-2-yl)-4,5,6,7-tetrahydroindol-4-one

HRID 1937631Notes

Reaction equation

HRID 1937631 reaction equation
Br[C:2]1[C:10]2[C:9](=[O:11])[CH2:8][C:7]([CH3:13])([CH3:12])[CH2:6][C:5]=2[N:4]([C:14]2[CH:19]=[CH:18][CH:17]=[CH:16][N:15]=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+]>COCCOC.O.C1C=CC([P]([Pd]([P](C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)([P](C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)[P](C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)=CC=1>[CH3:12][C:7]1([CH3:13])[CH2:6][C:5]2[N:4]([C:14]3[CH:19]=[CH:18][CH:17]=[CH:16][N:15]=3)[CH:3]=[C:2]([C:20]3[CH:25]=[CH:24][CH:23]=[CH:22][CH:21]=3)[C:10]=2[C:9](=[O:11])[CH2:8]1

Participants

7

Reactant 3

HCID 10340Sodium CarbonateHCID 66827Phenylboronic AcidHCID 224612763-Bromo-6,6-dimethyl-1-(pyridin-2-yl)-4,5,6,7-tetrahydroindol-4-one

Product 1

HCID 224612676,6-Dimethyl-3-phenyl-1-(pyridin-2-yl)-4,5,6,7-tetrahydroindol-4-oneYield 61.2%

Reagents, catalysts & solvents 3

HCID 178418397HCID 178418397, compoundCatalystHCID 962WaterSolventHCID 80711,2-DimethoxyethaneSolvent

Procedure

A solution of 3-bromo-6,6-dimethyl-1-(pyridin-2-yl)-4,5,6,7-tetrahydroindol-4-one (100 mg, 0.31 mmol), phenylboronic acid (153 mg, 1.25 mmol), tetrakis(triphenylphosphine)palladium (50 mg, 0.04 mmol) and Na2CO3 (197 mg, 1.9 mmol) in ethylene glycol dimethyl ether (10 mL) and water (4 mL) was heated at reflux for 8 h. The solvent was evaporated and the residue partitioned between DCM and aqueous K2CO3 (10% (w/v)). The organic layer was separated and the aqueous phase re-extracted with DCM (2×). The combined organic layers were washed with water, dried (MgSO4) and evaporated. The residue was chromatographed on silica gel, eluting with isohexane: EtOAc (9:1), to afford the title compound (60 mg, 61%) as a yellow solid. mp 160-162° C. Found: C, 78.23; H, 6.26; N, 8.57%. Calc. C21H20N2O.0.35(H2O): C, 78.16; H, 6.47; N, 8.68%. 1H NMR (360 MHz, CDCl3) δ 1.13 (6H,s), 2.45 (2H,s), 2.99 (2H,s), 7.17 (1H,s), 7.24-7.38 (5H,m), 7.67 (2H,d, J=7.2 Hz), 7.86 (1H,d of t, J=7.9 and 1.9 Hz), 8.56-8.61 (1H,m). MS (ES+) 317 (M+1).

Workup

  1. temperatureat reflux for 8 h
  2. customThe solvent was evaporated
  3. customthe residue partitioned between DCM and aqueous K2CO3 (10% (w/v))
  4. customThe organic layer was separated
  5. extractionthe aqueous phase re-extracted with DCM (2×)
  6. washThe combined organic layers were washed with water
  7. dry with materialdried (MgSO4)
  8. customevaporated
  9. customThe residue was chromatographed on silica gel
  10. washeluting with isohexane: EtOAc (9:1)

Sources & evidence

ORD record
ord-ccf5944504de4ab79b9b86aa1d798a3b
Source dataset
uspto-grants-2002_05
Patent number
US06395766B1

Reaction notes

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