Cesium fluoride → HCID 18182607, compound

HRID 1513916Notes

Reaction equation

HRID 1513916 reaction equation
[CH3:1][O:2][C:3]1[CH:4]=[C:5]2[C:10](=[CH:11][CH:12]=1)[C:9]([CH2:13][C:14]1[CH:19]=[CH:18][C:17]([O:20][CH2:21][CH2:22][N:23]3[CH2:28][CH2:27][CH2:26][CH2:25][CH2:24]3)=[CH:16][CH:15]=1)=[C:8](OS(C(F)(F)F)(=O)=O)[CH:7]=[CH:6]2.[F:37][C:38]1[CH:39]=[C:40](B(O)O)[CH:41]=[CH:42][CH:43]=1.[F-].[Cs+]>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>[F:37][C:38]1[CH:43]=[C:42]([C:8]2[CH:7]=[CH:6][C:5]3[C:10](=[CH:11][CH:12]=[C:3]([O:2][CH3:1])[CH:4]=3)[C:9]=2[CH2:13][C:14]2[CH:19]=[CH:18][C:17]([O:20][CH2:21][CH2:22][N:23]3[CH2:28][CH2:27][CH2:26][CH2:25][CH2:24]3)=[CH:16][CH:15]=2)[CH:41]=[CH:40][CH:39]=1

Participants

5

Reactant 3

HCID 25953Cesium fluorideHCID 27339863-Fluorophenylboronic acidHCID 57552542Trifluoromethanesulfonic acid 6-methoxy-1-[4-(2-piperidin-yl-ethoxy)-benzyl]-naphthalen-2-yl ester

Product 1

HCID 18182607HCID 18182607, compoundYield 63%

Reagents, catalysts & solvents 1

HCID 178418476HCID 178418476, compoundCatalyst

Conditions

Temperature
85 °C

Procedure

Charge a flask with trifluoromethanesulfonic acid 6-methoxy-1-[4-(2-piperidin-1-yl-ethoxy)-benzyl]-naphthalen-2-yl ester (2.0 g, 3.82 mmol), 3-fluorophenyl boronic acid (1.07 g, 7.64 mmol), trans-dichlorobis(triphenylphosphine)palladium II (536 mg, 0.76 mmol) and cesium fluoride (5.2 g, 34.4 mmol) along with 100 mL degassed acetonitrile and heat at 85° C. for 4 hours or until all the starting triflate is consumed. Cool the reaction, filter and purify on an SCX column eluting with 2N ammonia/methanol. The crude yield is 1.5 g (83%). Further purify the crude material on a silica column, eluting with 3% methanol/methylene chloride to give 1.1 g of the title compound (63%): 1H-NMR (CDCl3, 400 MHz) δ 7.81 (d, J=9.6 Hz, 1H); 7.73 (d, J=8.4 Hz, 1H); 7.39 (d, J=8.4 Hz, 1H); 7.28-7.25 (m, 1H); 7.19 (d, J=2.4 Hz, 1H); 7.11-7.06 (m, 2H); 7.04-7.01 (m, 2H); 6.88 (d, J=9.2 Hz, 2H); 6.75 (dd, J=6.4, 2.4 Hz, 2H); 4.34 (s, 2H); 4.07 (t, J=6.0 Hz, 2H); 3.93 (s, 3H); 2.81 (t, J=6.0 Hz, 2H); 2.57-2.57 (m, 4H); 1.67-1.61 (m, 4H); 1.48-1.46 (m, 2H).

Workup

  1. customdegassed acetonitrile
  2. customis consumed
  3. temperatureCool
  4. customthe reaction
  5. filtrationfilter
  6. custompurify on an SCX column
  7. washeluting with 2N ammonia/methanol
  8. customFurther purify the crude material on a silica column
  9. washeluting with 3% methanol/methylene chloride

Sources & evidence

ORD record
ord-0fa46360feca45efb0ced4cf0563ee6f
Source dataset
uspto-grants-2012_07
Patent number
US08217032B2

Reaction notes

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