Dichloromethane → HCID 16110523, compound

HRID 603415Notes

Reaction equation

HRID 603415 reaction equation
I[C:2]1[CH:27]=[CH:26][C:5]([O:6][CH2:7][CH2:8][CH2:9][O:10][C:11]2[CH:12]=[C:13]3[C:17](=[CH:18][CH:19]=2)[C@H:16]([CH2:20][C:21]([O:23][CH2:24][CH3:25])=[O:22])[CH2:15][CH2:14]3)=[CH:4][CH:3]=1.B1(B2OC(C)(C)C(C)(C)O2)OC(C)(C)C(C)(C)O1.C(Cl)Cl.CC([O-])=O.[K+].Br[C:55]1[CH:60]=[CH:59][CH:58]=[C:57]([CH3:61])[N:56]=1.C([O-])([O-])=O.[Na+].[Na+]>CN(C=O)C.Cl.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].C(Cl)Cl>[CH3:61][C:57]1[N:56]=[C:55]([C:2]2[CH:27]=[CH:26][C:5]([O:6][CH2:7][CH2:8][CH2:9][O:10][C:11]3[CH:12]=[C:13]4[C:17](=[CH:18][CH:19]=3)[C@H:16]([CH2:20][C:21]([O:23][CH2:24][CH3:25])=[O:22])[CH2:15][CH2:14]4)=[CH:4][CH:3]=2)[CH:60]=[CH:59][CH:58]=1

Participants

11

Reactant 6

HCID 6344DichloromethaneHCID 10340Sodium CarbonateHCID 792052-Bromo-6-methylpyridineHCID 517044Potassium AcetateHCID 2733548Bis(pinacolato)diboraneHCID 16110430HCID 16110430, compound

Product 1

HCID 16110523HCID 16110523, compoundYield 427.9%

Reagents, catalysts & solvents 4

HCID 6344DichloromethaneCatalystHCID 178418228Bis(cyclopenta-1,4-dien-1-yl(diphenyl)phosphane);dichloropalladium;iron(2+)Catalyst2×HCID 313Hydrochloric AcidSolventHCID 6228DimethylformamideSolvent

Conditions

Temperature
80 °C

Procedure

To a solution of ethyl {(1S)-5-[3-(4-iodophenoxy)propoxy]-2,3-dihydro-1H-inden-1-yl}acetate (70 mg, 0.15 mmol, Example 94) in DMF (1 mL), was added bis(pinacolato)diboron (41 mg, 0.16 mmol), PdCl2(dppf).CH2Cl2 (11 mg, 0.01 mmol), and KOAc (43 mg, 0.44 mmol). Argon was passed through the solution, and the reaction mixture was heated at 80° C. for 2 h, and then cooled to rt. More PdCl2(dppf).CH2Cl2 (5 mg, 0.005 mmol) was added, followed by the addition of 2-bromo-6-methylpyridine (50 mg, 0.29 mmol) and Na2CO3 (2 M aqueous solution, 0.37 mL). The reaction mixture was heated to 80° C. for 12 h, after which the reaction mixture was cooled to rt, diluted with HCl (1N aqueous solution) and extracted with EtOAc. The combined organic phases were dried, filtered, and concentrated under reduced pressure. Purification by a preparative thin layer chromatography (2:3 EtOAc/hexanes) gave 286 mg (40%) of the title compound. 1H NMR (400 MHz, CDCl3): δ 8.00 (d, 2H), 7.73-7.62 (m, 1H), 7.62-7.52 (m, 1H), 7.16-6.96 (m, 4H), 6.83 (s, 1H), 6.52 (d, 1H), 4.28-4.04 (m, 6H), 3.52-3.38 (m, 1H), 2.96-2.63 (m, 3H), 2.54 (s, 3H), 2.48-2.12 (m, 4H), 1.82-1.62 (m, 1H), 1.23 (t, 3H).

Workup

  1. temperaturecooled to rt
  2. temperatureThe reaction mixture was heated to 80° C. for 12 h
  3. temperatureafter which the reaction mixture was cooled to rt
  4. extractionextracted with EtOAc
  5. customThe combined organic phases were dried
  6. filtrationfiltered
  7. concentrationconcentrated under reduced pressure
  8. customPurification by a preparative thin layer chromatography (2:3 EtOAc/hexanes)

Sources & evidence

ORD record
ord-748a241520d640ecb4189474f87bf536
Source dataset
uspto-grants-2011_03
Patent number
US07906653B2

Reaction notes

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