1,2-Dimethoxyethane → 5-Pyrimidin-2-yl-indan-1-one

HRID 1913404Notes

Reaction equation

HRID 1913404 reaction equation
CC1(C)C(C)(C)OB([C:9]2[CH:10]=[C:11]3[C:15](=[CH:16][CH:17]=2)[C:14](=[O:18])[CH2:13][CH2:12]3)O1.Cl[C:21]1[N:26]=[CH:25][CH:24]=[CH:23][N:22]=1.C(COC)OC.C(=O)([O-])[O-].[Na+].[Na+]>C1C=CC(P(C2C=CC=CC=2)[C-]2C=CC=C2)=CC=1.C1C=CC(P(C2C=CC=CC=2)[C-]2C=CC=C2)=CC=1.Cl[Pd]Cl.[Fe+2].O>[N:22]1[CH:23]=[CH:24][CH:25]=[N:26][C:21]=1[C:9]1[CH:10]=[C:11]2[C:15](=[CH:16][CH:17]=1)[C:14](=[O:18])[CH2:13][CH2:12]2

Participants

7

Reactant 4

HCID 80711,2-DimethoxyethaneHCID 10340Sodium CarbonateHCID 744042-Chloropyrimidine2×HCID 185417105-(tetramethyl-1,3,2-dioxaborolan-2-yl)-2,3-dihydro-1H-inden-1-one

Product 1

HCID 584384795-Pyrimidin-2-yl-indan-1-oneYield 179.4%

Reagents, catalysts & solvents 2

HCID 178418228Bis(cyclopenta-1,4-dien-1-yl(diphenyl)phosphane);dichloropalladium;iron(2+)Catalyst2×HCID 962WaterSolvent

Conditions

Temperature
95 °C

Procedure

To a 500 mL round-bottomed flask was added 5-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)indan-1-one (SM-1a, 12.9 g, 35.0 mmol), 2-chloropyrimidine (4.00 g, 35.0 mmol) and 400 mL of dimethoxyethane. Dry nitrogen gas was bubbled through the solution for 10 minutes. Aqueous sodium carbonate (2M in water, 140 mmol) was added followed by Pd(dppf)Cl2 catalyst (100 mg, 0.12 mmol). The reaction mixture was degassed for another 15 minutes. The reaction was heated to 95° C. (silicon oil bath temperature) for 2 hours. A second aliquot of 2-chloropyrimidine (1 g, 8.73 mmol) and Pd(dppf)Cl2 (100 mg, 0.12 mmol) were added to the reaction and heating was continued for another 2 hours. The reaction was cooled to room temperature overnight and 200 mL of water was added. The mixture was filtered through a Celite® pad and the organic phase was separated. The aqueous phase was extracted with ethyl acetate. The combined organic phases were washed with brine, dried over anhydrous MgSO4 and evaporated to afford 13.2 g of an orange brown solid. This material was triturated with hexane to give 6.72 g of a light brown solid (SM-1b). The filtrate was concentrated and purified by silica chromatography (ethyl acetate/heptanes) on a Combiflash ISCO purification system (Teledyne Isco Inc., Lincoln, Nebr.) to afford another 600 mg of product (7.32 g, 98%). MS (ES+) 211.2 (M+H)+. 1H NMR (CDCl3) δ 2.77 (t, 2H), 3.24 (t, 2H), 7.28 (d, 1H), 7.87 (d, 1H), 8.48 (d, 1H), 8.57 (s, 1H), 8.87 (d, 2H).

Workup

  1. customDry nitrogen gas was bubbled through the solution for 10 minutes
  2. customThe reaction mixture was degassed for another 15 minutes
  3. temperatureheating
  4. temperatureThe reaction was cooled to room temperature overnight
  5. filtrationThe mixture was filtered through a Celite® pad
  6. customthe organic phase was separated
  7. extractionThe aqueous phase was extracted with ethyl acetate
  8. washThe combined organic phases were washed with brine
  9. dry with materialdried over anhydrous MgSO4
  10. customevaporated

Sources & evidence

ORD record
ord-620c126dab5b411880c4bebd376fa822
Source dataset
uspto-grants-2013_12
Patent number
US08609680B2

Reaction notes

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