Sodium Carbonate → HCID 10088766, compound

HRID 860858Notes

Reaction equation

HRID 860858 reaction equation
Br[C:2]1[CH:3]=[C:4]2[C:9](=[CH:10][CH:11]=1)[CH:8]=[C:7]([O:12][CH2:13][CH2:14][N:15]1[CH2:19][CH2:18][CH2:17][CH2:16]1)[CH:6]=[CH:5]2.[C:20]([C:22]1[CH:23]=[C:24](B(O)O)[CH:25]=[CH:26][CH:27]=1)#[N:21].C(=O)([O-])[O-].[Na+].[Na+]>Cl[Pd](Cl)([P](C1C=CC=CC=1)(C1C=CC=CC=1)C1C=CC=CC=1)[P](C1C=CC=CC=1)(C1C=CC=CC=1)C1C=CC=CC=1.C(O)(C)C>[N:15]1([CH2:14][CH2:13][O:12][C:7]2[CH:8]=[C:9]3[C:4](=[CH:5][CH:6]=2)[CH:3]=[C:2]([C:26]2[CH:27]=[C:22]([CH:23]=[CH:24][CH:25]=2)[C:20]#[N:21])[CH:11]=[CH:10]3)[CH2:19][CH2:18][CH2:17][CH2:16]1

Participants

6

Reactant 3

HCID 10340Sodium CarbonateHCID 27343253-Cyanophenylboronic acidHCID 100416631-{2-[(6-bromo-2-naphthyl)oxy]ethyl}pyrrolidine

Product 1

HCID 10088766HCID 10088766, compound

Reagents, catalysts & solvents 2

HCID 178418476HCID 178418476, compoundCatalystHCID 3776IsopropanolSolvent

Conditions

Temperature
85 °C

Procedure

A mixture of the product from Example 37B (35 mg, 0.11 mmol), 3-cyanophenylboronic acid (22 mg, 0.15 mmol), PdCl2(PPh3)2 (4.2 mg, 6 μmol), and isopropanol (0.5 mL) was treated with 2 M aqueous sodium carbonate (80 μL) and heated at 85° C. overnight. The mixture was cooled to room temperature and partitioned between 2 M aqueous NaOH and dichloromethane. The aqueous phase was separated and extracted with dichloromethane. The combined organic phases were filtered through diatomaceous earth, concentrated, and chromatographed through silica with a gradient of 0%/50%/50% to 10%/40%/50% methanol/ethyl acetate/dichloromethane followed by 8% methanol/dichloromethane to provide the title compound. 1HNMR (300 MHz, CD3OD) δ 1.86 (m, 4H), 2.73 (m, 4H), 3.01 (t, 2H), 4.28 (t, 2H), 7.22 (dd, 1H), 7.31 (d, 1H), 7.65 (t, 1H), 7.70 (dt, 1H), 7.75 (dd, 1H), 7.85–7.92 (m, 2H), 8.06 (dt, 1H), 8.07–8.13 (m, 2H); MS (ESI) m/z 343 (M+H)+.

Workup

  1. temperatureThe mixture was cooled to room temperature
  2. custompartitioned between 2 M aqueous NaOH and dichloromethane
  3. customThe aqueous phase was separated
  4. extractionextracted with dichloromethane
  5. filtrationThe combined organic phases were filtered through diatomaceous earth
  6. concentrationconcentrated
  7. customchromatographed through silica with a gradient of 0%/50%/50% to 10%/40%/50% methanol/ethyl acetate/dichloromethane

Sources & evidence

ORD record
ord-2a9be34361094510ae6f5df2c1f64936
Source dataset
uspto-grants-2006_12
Patent number
US07153889B2

Reaction notes

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