Cesium fluoride → HCID 67004412, compound

HRID 1513892Notes

Reaction equation

HRID 1513892 reaction equation
C[O:2][C:3]1[CH:4]=[C:5]2[C:10](=[CH:11][CH:12]=1)[C:9]([C:13](=[O:29])[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:38][C:39]1[C:44]([F:45])=[CH:43][CH:42]=[CH:41][C:40]=1B(O)O.[F-].[Cs+]>>[F:38][C:39]1[C:44]([F:45])=[CH:43][CH:42]=[CH:41][C:40]=1[C:8]1[CH:7]=[CH:6][C:5]2[C:10](=[CH:11][CH:12]=[C:3]([OH:2])[CH:4]=2)[C:9]=1[C:13]([C:14]1[CH:19]=[CH:18][C:17]([O:20][CH2:21][CH2:22][N:23]2[CH2:28][CH2:27][CH2:26][CH2:25][CH2:24]2)=[CH:16][CH:15]=1)=[O:29]

Participants

4

Reactant 3

HCID 25953Cesium fluorideHCID 2734333(2,3-Difluorophenyl)boronic acidHCID 11685250Trifluoromethanesulfonic acid 6-methoxy-1-[4-(2-piperidin-1-yl-ethoxy)benzoyl]-naphthalen-2-yl ester

Product 1

HCID 67004412HCID 67004412, compoundYield 72.1%

Conditions

Temperature
85 °C

Procedure

Charge a flask with trifluoromethanesulfonic acid 6-methoxy-1-[4-(2-piperidin-1-yl-ethoxy)-benzoyl]-naphthalen-2-yl ester (2.0 g, 3.7 mmol), 2,3 difluorophenyl boronic acid (1.17 g, 7.4 mmol) palladium dichloride bis(triphenylphosphine) (518 mg, 0.74 mmol) and cesium fluoride (5.06 g, 33.3 mmol) and add 250 mL degassed acetonitrile. Heat the mixture at 85° C. for two hours, cool the reaction and filter off any solids. Purify on an SCX column eluting with 2N ammonia/methanol. Purify further on a silica gel column eluting with a 0-10% methanol/methylene chloride gradient to give 1.3 g (70%) of the title compound: 1H-NMR (CD3OD, 400 MHz) δ7.92 (d, J=8.8 Hz, 1H); 7.54 (dd, J=8.4, 4.0 Hz, 3H); 7.43 (dd, J=8.4, 1.6 Hz, 1H); 7.31 (d, J=2.8 Hz, 1H); 7.09 (dd, J=9.2, 2.4 Hz, 1H); 7.05-6.92 (m, 3H); 6.79 (d, J=8.8 Hz, 2H); 4.10 (t, J=5.6 Hz, 2H); 3.93 (s, 3H); 2.73 (t, J=5.2 Hz, 2H); 2.50-2.50 (m, 4H); 1.62-1.57 (m, 4H); 1.48-1.43 (m, 2H).

Workup

  1. additionadd 250 mL
  2. customdegassed acetonitrile
  3. temperaturecool
  4. customthe reaction
  5. filtrationfilter off any solids
  6. customPurify on an SCX column
  7. washeluting with 2N ammonia/methanol
  8. customPurify further on a silica gel column
  9. washeluting with a 0-10% methanol/methylene chloride gradient

Sources & evidence

ORD record
ord-fa24f74664954f178cd60eaf1f85ab8d
Source dataset
uspto-grants-2012_07
Patent number
US08217032B2

Reaction notes

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